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2010s
2017
Treatment Approved
FDA APPROVES PEMBROLIZUMAB FOR ADULT AND PEDIATRIC LYMPHOMA
Details
March 14, 2017
Treatment Approved
FDA APPROVES PEMBROLIZUMAB FOR ADULT AND PEDIATRIC LYMPHOMA

The FDA granted accelerated approval to pembrolizumb (Keytruda), an anti-PD-1 checkpoint inhibitor, for both adult and pediatric patients with refractory or relapsed classical Hodgkin lymphoma (cHL).

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2017
Treatment Approved
FDA APPROVES NIVOLUMAB FOR BLADDER CANCER
Details
February 01, 2017
Treatment Approved
FDA APPROVES NIVOLUMAB FOR BLADDER CANCER

The FDA granted accelerated approval to nivolumab (Opdivo), an anti-PD-1 checkpoint inhibitor, for patients with advanced urolthelial carcinoma, the most common form of bladder cancer. 

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2016
Treatment Approved
FDA APPROVES EXPANDED ACCESS TO DARATUMUMAB FOR MYELOMA
Details
November 20, 2016
Treatment Approved
FDA APPROVES EXPANDED ACCESS TO DARATUMUMAB FOR MYELOMA
The FDA approved expanded access to daratumumab (Darzalex), a targeted antibody against the CD38 receptor, for patients with multiple myeloma. Previously, daratumumab was available for patients who had received at least 3 priopr therapies. Now, myeloma patients who have received 1 prior therapy can receive daratumumab.
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2016
Treatment Approved
FDA APPROVES NIVOLUMAB FOR HEAD AND NECK CANCER
Details
November 09, 2016
Treatment Approved
FDA APPROVES NIVOLUMAB FOR HEAD AND NECK CANCER

The FDA granted approval to nivolumab (Opdivo), an anti-PD-1 checkpoint inhibitor, for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that has progressed despite platinum-based chemotherapy. 

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2016
Treatment Approved
FDA APPROVES PEMBROLIZUMAB FOR LUNG CANCER
Details
October 23, 2016
Treatment Approved
FDA APPROVES PEMBROLIZUMAB FOR LUNG CANCER

The FDA granted approval to pembrolizumab (Keytruda), a anti-PD-1 checkpoint inhibitor, for metastatic non-small cell lung cancer patients whose tumors express PD-L1.

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2016
Treatment Approved
FDA APPROVES OLARATUMAB FOR SARCOMA
Details
October 18, 2016
Treatment Approved
FDA APPROVES OLARATUMAB FOR SARCOMA

The FDA granted approval to olaratumab (LARTRUVO), a targeted antibody against the PDGFRα, for patients with soft tissue sarcoma (STS) for whom surgery and radiation therapy are not effective options.

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2016
Treatment Approved
FDA APPROVES ATEZOLIZUMAB FOR LUNG CANCER
Details
October 17, 2016
Treatment Approved
FDA APPROVES ATEZOLIZUMAB FOR LUNG CANCER

The FDA granted approval to atezolizumab (TECENTRIQ), and anti-PD-L1 checkpoint inhibitor, for patients with metastatic, chemotherapy-resistant non-small cell lung cancer (NSCLC).

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2016
Treatment Approved
FDA APPROVES PEMBROLIZUMAB FOR HEAD AND NECK CANCER
Details
August 04, 2016
Treatment Approved
FDA APPROVES PEMBROLIZUMAB FOR HEAD AND NECK CANCER

The FDA granted accelerated approval to pembrolizumab (Keytruda), an anti-PD-1 checkpoint inhibitor, for patients with recurrent or metastatc head and neck squamous cell carcinoma (HNSCC).

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2016
Treatment Approved
FDA APPROVES ATEZOLIZUMAB FOR BLADDER CANCER
Details
May 17, 2016
Treatment Approved
FDA APPROVES ATEZOLIZUMAB FOR BLADDER CANCER

The FDA granted accelerated approval for atezolizumab (Tecentriq), a checkpoint inhibitor that targets the PD-1 pathway, to treat the most common type of bladder cancer. This is the first approved anti-PD-1/PD-L1 checkpoint inhibitor that targets the PD-L1 ligand as opposed to the PD-1 receptor.

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2016
Treatment Approved
FDA APPROVES NIVOLUMAB FOR LYMPHOMA
Details
May 16, 2016
Treatment Approved
FDA APPROVES NIVOLUMAB FOR LYMPHOMA

The FDA granted accelerated approval to nivolumab (Opdivo), an anti-PD-1 checkpoint inhibitor, for patients with classical Hodgkin lymphoma (cHL) whose disease has relapsed or progressed after stem cell transplantation and the targeted antibody brentuximab vedotin (Adcetris).

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2016
Treatment Approved
FDA APPROVES OBINUTUZUMAB FOR LMYPHOMA
Details
February 25, 2016
Treatment Approved
FDA APPROVES OBINUTUZUMAB FOR LMYPHOMA

The FDA granted approval to obinutuzumab (GAZYVA), a targeted antibody against CD20, for patients with follicular lymphoma.

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2016
Treatment Approved
FDA APPROVES OFATUMUMAB FOR LEUKEMIA
Details
January 18, 2016
Treatment Approved
FDA APPROVES OFATUMUMAB FOR LEUKEMIA

The FDA granted approval to ofatumumab (ARZERRA), a targeted antibody against CD20, for patients with chronic lymphocytic leukemia (CLL) who are in complete or partial response after at least two lines of therapy.

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2015
Treatment Approved
FDA APPROVES SECOND MONOCLONAL ANTIBODY FOR MULTIPLE MYELOMA
Details
November 30, 2015
Treatment Approved
FDA APPROVES SECOND MONOCLONAL ANTIBODY FOR MULTIPLE MYELOMA

The FDA approved elotuzumab (Empliciti) for patients with multiple myeloma. Elotuzumab targets the SLAM7 receptor, which is present on both myeloma cells and the immune system's natural killer (NK) cells. By attaching to the myeloma cells, it marks them for destruction, and by attaching to NK cells, it primes the immune cells to search for and attack the myeloma cells

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2015
Treatment Approved
NIVOLUMAB BECOMES FIRST FDA-APPROVED CHECKPOINT BLOCKADE FOR KIDNEY CANCER
Details
November 23, 2015
Treatment Approved
NIVOLUMAB BECOMES FIRST FDA-APPROVED CHECKPOINT BLOCKADE FOR KIDNEY CANCER

kidney-cancer-nivolumab-immunotherapy-treatment-446x150.jpgNew hope now exists for patients with advanced kidney cancer. On November 23, 2015, the FDA approved the immunotherapy drug nivolumab (Opdivo®, Bristol-Myers Squibb) to treat metastatic renal cell carcinoma (RCC)—the most common form of kidney cancer—that has failed to respond to a previous treatment.

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2015
Treatment Approved
FIRST MONOCLONAL ANTIBODY FOR MULTIPLE MYELOMA RECEIVES FDA APPROVAL
Details
November 16, 2015
Treatment Approved
FIRST MONOCLONAL ANTIBODY FOR MULTIPLE MYELOMA RECEIVES FDA APPROVAL

daratumumab-206x136.jpgMultiple myeloma patients got some good news on November 16—the immunotherapy daratumumab (Darzalex®) was given approval by the FDA for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy. It is the first monoclonal antibody ever approved for multiple myeloma.

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2015
Treatment Approved
OPDIVO (NIVOLUMAB) FDA APPROVED FOR LUNG CANCER
Details
November 13, 2015
Treatment Approved
OPDIVO (NIVOLUMAB) FDA APPROVED FOR LUNG CANCER

opdivo_206x136.jpgThe FDA approved Opdivo® (nivolumab) for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) after prior therapy. Opdivo is the first immunotherapy agent approved for the treatment of lung cancer.

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2015
Treatment Approved
FDA APPROVES FIRST IN A NEW CLASS OF IMMUNOTHERAPIES
Details
October 27, 2015
Treatment Approved
FDA APPROVES FIRST IN A NEW CLASS OF IMMUNOTHERAPIES

oncolytic-virus-illustration-446x150.jpgOn October 27, 2015, the FDA approved a new type of immunotherapy for the treatment of advanced melanoma. Called talimogene laherparepvec (Imlygic™), and made by Amgen, the immunotherapy is an oncolytic virus therapy. This is a genetically engineered virus that has been tweaked to preferentially kill cancer cells. In the case of Imlygic, the virus is a modified version of the herpes simplex virus I, the virus that causes cold sores.

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2015
Treatment Approved
FDA APPROVES EXPANDED USE OF NIVOLUMAB FOR LUNG CANCER
Details
October 09, 2015
Treatment Approved
FDA APPROVES EXPANDED USE OF NIVOLUMAB FOR LUNG CANCER

On October 9, 2015, the FDA expanded its approval of nivolumab to include patients with non-squamous NSCLC that has stopped responding to chemotherapy. Approximately 85% of NSCLC cases are the non-squamous type.

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2015
Treatment Approved
FDA APPROVES PD-1 IMMUNOTHERAPY FOR MOST COMMON TYPE OF LUNG CANCER
Details
October 02, 2015
Treatment Approved
FDA APPROVES PD-1 IMMUNOTHERAPY FOR MOST COMMON TYPE OF LUNG CANCER

On October 2, 2015, the FDA approved the immunotherapy drug pembrolizumab (Keytruda®), made by Merck, as second-line treatment for patients with lung cancer, the leading cause of cancer-related death in the U.S. and the world. Pembrolizumab is approved for the treatment of both squamous and non-squamous non-small cell lung cancer (NSCLC) that is no longer responding to standard-of-care chemotherapy. Together, these types account for the vast majority of lung cancer cases.

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2015
Treatment Approved
IN A FIRST, FDA APPROVES IMMUNOTHERAPY COMBINATION FOR ADVANCED MELANOMA
Details
October 01, 2015
Treatment Approved
IN A FIRST, FDA APPROVES IMMUNOTHERAPY COMBINATION FOR ADVANCED MELANOMA

On October 1, 2015, the FDA announced accelerated approval of a combination of immunotherapy drugs for the frontline treatment of advanced melanoma. The drugs, ipilimumab (Yervoy®) and nivolumab (Opdivo®), made by Bristol-Myers Squibb (BMS), are two immune checkpoint inhibitors that “release the brakes” on the immune system, allowing it to mount a stronger and more effective attack against cancer. The FDA based its approval on results from a clinical trial showing that patients who received the combination had better responses than those who received ipilimumab alone.

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2014
Major Discovery
NIVOLUMAB AND IPILIMUMAB: 90% RESPONSE RATE IN MELANOMA
Details
November 13, 2014
Major Discovery
NIVOLUMAB AND IPILIMUMAB: 90% RESPONSE RATE IN MELANOMA
Mario Sznol announces one- and two-year survival rates of 94% and 88% from a phase Ib trial of nivolumab, a PD-1 checkpoint inhibitor, and ipilimumab (Yervoy®) in advanced melanoma.[i]

[i] http://news.yale.edu/2014/06/02/long-term-results-encouraging-combination-immunotherapy-advanced-melanoma
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2014
Major Discovery
CAR T CELL THERAPY ACHIEVES 92% RESPONSE RATE
Details
November 13, 2014
Major Discovery
CAR T CELL THERAPY ACHIEVES 92% RESPONSE RATE
Steven A. RosenbergCRI CONNECTIONPOSTDOC SPONSORCOLEY AWARD announces successful data from its phase 1/2a clinical trial of patients with aggressive non-Hodgkins lymphoma. They treated patients with its an anti-CD19 chimeric antigen receptor (CAR) T cell therapy called KTE-C19. Eight of 13 patients with advanced B cell malignancies showed complete remissions, while four showed partial remissions. The total result was a 92% objective response rate. Furthermore, four of seven patients with chemotherapy-refractory diffuse large B-cell Lymphoma showed complete remissions. Three of these cases are ongoing, while one is ongoing after 22 months. The first report to our knowledge of successful treatment of DLBCL with anti-CD19 CAR T cells.[i]

[i] Kochenderfer JN, Dudley ME, Kassim SH, Somerville RP, Carpenter RO, Stetler-Stevenson M, Yang JC, Phan GQ, Hughes MS, Sherry RM, Raffeld M, Feldman S, Lu L, Li YF, Ngo LT, Goy A, Feldman T, Spaner DE, Wang ML, Chen CC, Kranick SM, Nath A, Nathan DA, Morton KE, Toomey MA, Rosenberg SA. Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated With Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor. J Clin Oncol 2014 Aug 25. (PMID: 25154820)
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2014
Major Discovery
THE ONTOGENY OF TUMOR-ASSOCIATED MACROPHAGES
Details
November 13, 2014
Major Discovery
THE ONTOGENY OF TUMOR-ASSOCIATED MACROPHAGES
Ming Li, Eric Pamer, and colleagues show that mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). Depletion of tumor-associated macrophages, but not mammary tissue macrophages, restores tumor-infiltrating cytotoxic T cell responses and suppresses tumor growth. These findings reveal the ontogeny of tumor-associated macrophages and a discrete tumor-elicited inflammatory response, which may provide new opportunities for cancer immunotherapy.[i]

[i] Franklin RA, Liao W, Sarkar A, Kim MV, Bivona MR, Liu K, Pamer EG, Li MO. The cellular and molecular origin of tumor-associated macrophages. Science 2014 May 23; 344 (6186): 921-5. Epub 2014 May 8. (PMID: 24812208)
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2014
Treatment Approved
FDA APPROVES CYRAMZA FOR STOMACH CANCER
Details
November 13, 2014
Treatment Approved
FDA APPROVES CYRAMZA FOR STOMACH CANCER
The U.S. Food and Drug Administration (FDA) approves Cyramza (ramucirumab) to treat advanced stomach cancer and gastroesophageal junction adenocarcinoma, a type of cancer located where the stomach connects to the esophagus. Patients in a clinical trial who took the drug lived on average 1.4 months longer than patients who did not take it.
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2014
CRI Milestone
CRI LAUNCHES THEANSWERTOCANCER.ORG FOR PATIENTS AND CAREGIVERS
Details
November 13, 2014
CRI Milestone
CRI LAUNCHES THEANSWERTOCANCER.ORG FOR PATIENTS AND CAREGIVERS

the-answer-to-cancer-logo-206x136.jpgThe Cancer Research Institute launches the first-of-its-kind website devoted to cancer immunotherapy designed specifically for cancer patients and their caregivers. Through TheAnswerToCancer.org, CRI seeks to engage, educate, and empower patients and their loved ones to learn more about cancer immunotherapy as a treatment option across numerous tumor types. The site provides a robust but accessible overview of the science behind cancer immunotherapy, detailed information about cancer immunotherapy clinical trials, and voices from the cancer immunotherapy community

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2014
Major Discovery
NEW TREATMENT STRATEGY COAXES CANCER OUT OF HIDING
Details
November 13, 2014
Major Discovery
NEW TREATMENT STRATEGY COAXES CANCER OUT OF HIDING
Kunle Odunsi and colleagues show that a drug called decitabine increases the effectiveness of a vaccine designed to elicit an immune response against ovarian cancer.[i]

[i] Odunsi K, Matsuzaki J, James SR, Mhawech-Fauceglia P, Tsuji T, Miller A, Zhang W, Akers SN, Griffiths EA, Miliotto A, Beck A, Batt CA, Ritter G, Lele S, Gnjatic S, Karpf AR. Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer. Cancer Immunol Res 2014 Jan; 2 (1): 37-49. (PMID: 24535937)
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2014
CRI Milestone
COLEY TO CURE: CRI PUBLISHES 60-YEAR RETROSPECTIVE
Details
November 13, 2014
CRI Milestone
COLEY TO CURE: CRI PUBLISHES 60-YEAR RETROSPECTIVE

Coley-to-Cure.jpgColey to Cure shows that the story of the Cancer Research Institute is the story of cancer immunotherapy. This 48-page retrospective helps readers understand the central role that CRI has played in bringing the field of cancer immunology to its current era of fruition, and what it is doing to set the pace for the future. 

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2014
Field Milestone
NIVOLUMAB IS APPROVED IN JAPAN UNDER THE NAME OPDIVO
Details
November 13, 2014
Field Milestone
NIVOLUMAB IS APPROVED IN JAPAN UNDER THE NAME OPDIVO

opdivo-86174642.jpgThe promising immunotherapy drug nivolumab received its first regulatory approval in July for use in inoperable melanoma in Japan, under the name Opdivo. This makes it the first anti-PD-1 cancer therapy to clear this hurdle.

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2014
Major Discovery
NEWS FOR PANCREATIC CANCER
Details
November 13, 2014
Major Discovery
NEWS FOR PANCREATIC CANCER
Elizabeth Jaffee and colleagues demonstrate a survival benefit in pancreatic cancer patients receiving the combination of GVAX Pancreas and CRS-207 cancer vaccines in a phase II trial.[i] The median overall survival of the patients receiving the combination was 6.1 months compared to 3.9 months. In July, it is given "Breakthrough Therapy" designation from the FDA.

[i] Le DT, Wang-Gillam A, Picozzi V, Greten TF, Crocenzi TS, Springett GM, Morse M, Zeh H, Cohen DJ, Fine RL, Onners B, Uram JN, Laheru D, Murphy A, Skoble J, Lemmens E, Grous JJ, Dubensky T, Brockstedt DG, Jaffee EM. A phase 2, randomized trial of GVAX pancreas and CRS-207 immunotherapy versus GVAX alone in patients with metastatic pancreatic adenocarcinoma: Updated results. J Clin Oncol 32, 2014 (suppl 3; abstr 177^).
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2014
Field Milestone
FDA APPROVES NEW CANCER IMMUNOTHERAPY
Details
November 13, 2014
Field Milestone
FDA APPROVES NEW CANCER IMMUNOTHERAPY

2014-09-04-FDA-Approves-Merck-Immunotherapy-500x300_1.jpgThe FDA announced that Merck's Keytruda (pembrolizumab) was granted accelerated approval for advanced or unresectable melanoma, making it the first PD-1 inhibitor cleared in the US.

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2014
Treatment Approved
BLINATUMOMAB IS FDA APPROVED, MAKING IT THE FIRST APPROVED BITE IN THE U.S.
Details
November 13, 2014
Treatment Approved
BLINATUMOMAB IS FDA APPROVED, MAKING IT THE FIRST APPROVED BITE IN THE U.S.

site-content-logo-blincyto.pngThe FDA approves Blincyto (blinatumomab) for use in the treatment of B cell acute lymphoblastic leukemia (ALL). The drug, manufactured by Amgen, is the first of a novel class of agents known as bispecific T cell engagers (BiTE), which consist of two monoclonal antibodies joined together. One end of the BiTE binds to a molecule on T cells, and the other end binds to a molecule on cancer cells; by bringing the two together, the BiTE facilitates cancer cell killing. Blincyto (blinatumomab) is designed to treat cancers expressing a molecule called CD19—found on the surface of B cell ALL and also non-Hodgkin’s lymphoma. The FDA approval was based on a phase II clinical trial showing that, of the 185 patients evaluated, 41.6% achieved complete remission with Blincyto.

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2014
Treatment Approved
OPDIVO (NIVOLUMAB) APPROVED BY THE FDA
Details
November 13, 2014
Treatment Approved
OPDIVO (NIVOLUMAB) APPROVED BY THE FDA

The FDA approved Opdivo® (nivolumab) for melanoma patients. Opdivo, made by Bristol-Myers Squibb (BMS), belongs to a class of immunotherapies called checkpoint inhibitors. BMS’s Opdivo is the second FDA-approved checkpoint inhibitor targeted at an immune protein called PD-1. Opdivo is FDA-approved for treating metastatic melanoma in patients who have failed prior treatment. Ongoing studies suggest it may benefit patients with many different cancers, including lung, brain, head and neck, stomach, and kidney cancers.

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2013
Major Discovery
CAR T CELL THERAPY ACHIEVES 89% RESPONSE RATE
Details
November 13, 2013
Major Discovery
CAR T CELL THERAPY ACHIEVES 89% RESPONSE RATE
Carl H. June, Michael Kalos, and colleagues achieve a response rate of 89% in adults and children with acute lymphoblastic leukemia (ALL), using genetically modified T cells from a patient’s own body to attack and kill cancer cells.[i]

[i] Grupp S, Frey NV, Aplenc R, Barrett DM, Chew A, Kalos M, Levine BL, Litchman M, Maude SL, Rheingold SR, Shen A, Strait C, Teachey DT, Wood PA, Porter D, June CH. T cells engineered with a chimeric antigen receptor (CAR) targeting CD19 (CTL019) produce significant in vivo proliferation, complete responses, and long-term persistence without GVHD in children and adults with relapsed, refractory ALL. ASH Annual Meeting. Abstract 168. Presented December 8, 2013.
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2013
Major Discovery
GUT MICROBIOTA HELP SHAPE THE ANTI-CANCER IMMUNE RESPONSE
Details
November 13, 2013
Major Discovery
GUT MICROBIOTA HELP SHAPE THE ANTI-CANCER IMMUNE RESPONSE
In two publications, Laurence Zitvogel, Guido Kroemer, and colleagues[i] and Giorgio Trinchieri, Yasmine Belkaid, and colleagues[ii] demonstrate that gut microbiota help shape the anti-cancer immune response by mediating its effects on the tumor microenvironment.

[i] Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillère R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ, Schlitzer A, Ginhoux F, Apetoh L, Chachaty E, Woerther PL, Eberl G, Bérard M, Ecobichon C, Clermont D, Bizet C, Gaboriau-Routhiau V, Cerf-Bensussan N, Opolon P, Yessaad N, Vivier E, Ryffel B, Elson CO, Doré J, Kroemer G, Lepage P, Boneca IG, Ghiringhelli F, Zitvogel L. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 2013 Nov 22; 342 (6161): 971-6. (PMID: 24264990)

[ii] Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA, Molina DA, Salcedo R, Back T, Cramer S, Dai RM, Kiu H, Cardone M, Naik S, Patri AK, Wang E, Marincola FM, Frank KM, Belkaid Y, Trinchieri G, Goldszmid RS. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 2013 Nov 22; 342 (6161): 967-70. (PMID: 24264989)
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2013
CRI Milestone
CRI BRINGS TWO IMMUNOTHERAPIES TO A CLINICAL TRIAL
Details
November 13, 2013
CRI Milestone
CRI BRINGS TWO IMMUNOTHERAPIES TO A CLINICAL TRIAL
Through CRI’s Clinical Accelerator program, two new checkpoint inhibitor drugs, MEDI4736 (anti-PD-L1) and tremelimumab (anti-CTLA-4), are being tested in a phase I trial for patients with six different cancer types, including colorectal cancer, cervical cancer, head and neck cancer, kidney cancer, lung cancer, and ovarian cancer. This will be one of the first combination immunotherapies combining these drugs in several cancer types.
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2013
CRI Milestone
CRI PRESENTS THE COLEY AND ALT AWARDS
Details
November 13, 2013
CRI Milestone
CRI PRESENTS THE COLEY AND ALT AWARDS
CRI presents the 2013 William B. Coley Award to Michael Karin for his groundbreaking work on the role of chronic inflammation in the development of tumors. CRI also presents the annual Frederick W. Alt Award for New Discoveries in Immunology to former CRI postdoctoral fellow Jill O'donnell-Tormey, who has been the chief executive of CRI for more than 20 years. 
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2013
Major Discovery
A BIOMARKER FOR IPILIMUMAB (YERVOY)
Details
November 13, 2013
Major Discovery
A BIOMARKER FOR IPILIMUMAB (YERVOY)
Padmanee Sharma discovered a biomarker— ICOS+ CD4 T cells—to identify melanoma patients who are more likely to respond to ipilimumab (Yervoy®).[i]

[i] Ng Tang D, Shen Y, Sun J, Wen S, Wolchok JD, Yuan J, Allison JP, Sharma P. Increased frequency of ICOS+ CD4 T cells as a pharmacodynamic biomarker for anti-CTLA-4 therapy. Cancer Immunol Res 2013 Oct; 1 (4): 229-34. Epub 2013 Jul 31. (PMID: 24777852)
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2013
Major Discovery
UNIVERSAL METHOD FOR AUGMENTING CANCER ANTIBODIES
Details
November 13, 2013
Major Discovery
UNIVERSAL METHOD FOR AUGMENTING CANCER ANTIBODIES
K. Christopher Garcia, Irving L. Weissman, and colleagues show that they were able to potently antagonize CD47 on cancer cells, but did not induce macrophage phagocytosis on their own. Instead, they exhibited remarkable synergy with all tumor-specific monoclonal antibodies tested by increasing phagocytosis in vitro and enhancing anti-tumor responses in vivo. This "one-two punch" directs immune responses against tumor cells while lowering the threshold for macrophage activation, thereby providing a universal method for augmenting the efficacy of therapeutic anticancer antibodies.[i]

[i] Weiskopf K, Ring AM, Ho CC, Volkmer JP, Levin AM, Volkmer AK, Ozkan E, Fernhoff NB, van de Rijn M, Weissman IL, Garcia KC. Engineered SIRPα variants as immunotherapeutic adjuvants to anticancer antibodies. Science 2013 Jul 5; 341 (6141): 88-91. Epub 2013 May 30. (PMID: 23722425)
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2013
Major Discovery
CAR T CELL THERAPY ATTAINS COMPLETE RESPONSES IN LEUKEMIA
Details
November 13, 2013
Major Discovery
CAR T CELL THERAPY ATTAINS COMPLETE RESPONSES IN LEUKEMIA
Michel Sadelain, Renier Brentjens, Isabelle Riviere, and colleagues treat five adult patients with relapsed B cell acute lymphoblastic leukemia (B-ALL) with chimeric antigen receptor (CAR) T cell transfer and all patients had a complete response, forming a highly effective bridge to potentially curative therapy with subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT).[i]

[i] Brentjens RJ1, Davila ML, Riviere I, Park J, Wang X, Cowell LG, Bartido S, Stefanski J, Taylor C, Olszewska M, Borquez-Ojeda O, Qu J, Wasielewska T, He Q, Bernal Y, Rijo IV, Hedvat C, Kobos R, Curran K, Steinherz P, Jurcic J, Rosenblat T, Maslak P, Frattini M, Sadelain M. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 2013 Mar 20; 5 (177): 177ra38. (PMID: 23515080)
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2013
Major Discovery
MONTANIDE PRODUCES CD8+ T CELL DYSFUNCTION
Details
November 13, 2013
Major Discovery
MONTANIDE PRODUCES CD8+ T CELL DYSFUNCTION
Willem Overwijk, Patrick Hwu, and colleagues demonstated that Montanide (incomplete Freund's adjuvant), which is used in a number of cancer vaccines, can induce specific T cell sequestration, dysfunction, and deletion at vaccination sites.[i]

[i] Hailemichael Y, Dai Z, Jaffarzad N, Ye Y, Medina MA, Huang XF, Dorta-Estremera SM, Greeley NR, Nitti G, Peng W, Liu C, Lou Y, Wang Z, Ma W, Rabinovich B, Sowell RT, Schluns KS, Davis RE, Hwu P, Overwijk WW. Persistent antigen at vaccination sites induces tumor-specific CD8⁺ T cell sequestration, dysfunction and deletion. Nat Med 2013 Apr; 19 (4): 465-72.Epub 2013 Mar 3. (PMID: 23455713)
 
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2013
Field Milestone
INAUGURAL ISSUE OF AACR CANCER IMMUNOLOGY RESEARCH PUBLISHED
Details
November 13, 2013
Field Milestone
INAUGURAL ISSUE OF AACR CANCER IMMUNOLOGY RESEARCH PUBLISHED

CIR.gifCancer Immunology Research, the newest publication of the American Association for Cancer Research (AACR), is published. As a new collaboration with Cancer Research Institute (CRI), Cancer Immunity will publish its final issue and Cancer Immunology Research will continue to publish cutting-edge research in cancer immunology. All content of Cancer Immunity, founded in 2001, will be posted on the Cancer Immunology Research website, allowing readers to access content for both journals in one location.

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2013
Field Milestone
CANCER IMMUNOTHERAPY "BREAKTHROUGH OF THE YEAR"
Details
November 13, 2013
Field Milestone
CANCER IMMUNOTHERAPY "BREAKTHROUGH OF THE YEAR"
Science magazine—America’s leading scientific journal—has deemed cancer immunotherapy the 2013 “breakthrough of the year,” beating out nine other contenders. The editors of Science called 2013 a “turning point in cancer,” as results from several recent clinical trials have documented the power of the immunotherapeutic approach to treating cancer, including very advanced and metastatic disease.

http://news.sciencemag.org/breakthrough-of-the-year-2013
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2013
CRI Milestone
CANCER IMMUNOTHERAPY AWARENESS MONTH LAUNCHED
Details
June 01, 2013
CRI Milestone
CANCER IMMUNOTHERAPY AWARENESS MONTH LAUNCHED

CIAM-banner-WHITE-Curing-All-Cancers_446x175_1.jpgWith enthusiasm for cancer immunotherapy mounting thanks to recent successes in the clinic with immune-based cancer treatments such as anti-CTLA-4 and anti-PD-1 antibodies, and the FDA approvals of sipuleucel-T prostate cancer vaccine and ipilimumab for the treatment of melanoma, and in light of the many promising immunotherapies now in clinical trials with potential for near-term FDA approval, the Cancer Research Institute launched the first annual Cancer Immunotherapy Awareness Month in June 2013 as a way to increase public awareness of the power of immunotherapy to revolutionize cancer treatment and of the need for continued public support for research to bring these treatments to more patients sooner. The inauguaral month featured a series of five webinars from leading experts in the field, including Kunle Odunsi, M.D., Ph.D., Carl H. June, M.D., Elizabeth Jaffee, M.D., Jedd D. Wolchok, M.D., Ph.D., and Philip Greenberg, M.D., who provided first-hand perspectives on the impact immunotherapy is having on cancer patient treatment. The month also included Wear White for a Cure Day™ on June 7, a day-long awareness and fundraising event. The month also included a ceremony for planting white flowers (baby dragon wing begonias) along the Park Avenue malls, and a month-long retail event with 1-800-FLOWERS.COM®.

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2012
Major Discovery
REGULATORY T CELLS PLAY ROLE IN PRIMING OF IMMUNE RESPONSES
Details
November 13, 2012
Major Discovery
REGULATORY T CELLS PLAY ROLE IN PRIMING OF IMMUNE RESPONSES
Sebastian Amigorena and colleagues demonstrate that regulatory T cells (Tregs) play a critical role during the priming of immune responses. Treg depletion induces the activation and expansion of a population of low-avidity CD8+ T cells, which stabilized the interactions between antigen-presenting dendritic cells and low-avidity T cells. These results suggest that Tregs are important regulators of the homeostasis of CD8+ T cell priming and play a critical role in the induction of high-avidity primary responses and effective memory.[i]

[i] Pace L, Tempez A, Arnold-Schrauf C, Lemaitre F, Bousso P, Fetler L, Sparwasser T, Amigorena S. Regulatory T cells increase the avidity of primary CD8+ T cell responses and promote memory. Science 2012 Oct 26; 338 (6106): 532-6. (PMID: 23112334)
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2012
CRI Milestone
CRI FUNDS "DREAM TEAM" OF CANCER IMMUNOLOGISTS
Details
November 13, 2012
CRI Milestone
CRI FUNDS "DREAM TEAM" OF CANCER IMMUNOLOGISTS
CRI has partnered with the nonprofit Stand Up To Cancer (SU2C) to fund a “Dream Team” of researchers working to develop the next frontier of cancer immunology. The group consists of several of the field’s leading lights, including James P. Allison, Cassian Yee, Antoni Ribas, and Drew Pardoll. The team will be performing clinical and laboratory research centered around two key areas of immunotherapy, checkpoint blockade and adoptive cell transfer. Several of the trials are now accruing patients and others are schedule to open later this year.
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2012
Field Milestone
FIELD-WIDE INITIATIVE ON T CELL ASSAY REPORTING COMPLETED
Details
November 13, 2012
Field Milestone
FIELD-WIDE INITIATIVE ON T CELL ASSAY REPORTING COMPLETED

2012-07-26_Community-wide-consensus.jpgMembers of CRI’s Cancer Immunotherapy Consortium (CIC) and the Immunoguiding Program (CIP) of the Germany-based Association for Cancer Immunotherapy (CIMT) announce the completion of the Minimal Information About T cell Assays (MIATA) Project to establish baseline requirements for reporting the results of T cell immune monitoring in clinical trials. The new guidelines promise to help accelerate progress in cancer immunotherapy development by making data interpretation and comparison easier for investigators and regulatory agencies.
 

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2012
Major Discovery
CD8+ T CELLS HAVE A TOLERANCE-SPECIFIC GENE PROFILE
Details
November 13, 2012
Major Discovery
CD8+ T CELLS HAVE A TOLERANCE-SPECIFIC GENE PROFILE
Andrea Schietinger, Philip Greenberg, and colleagues show that tolerant CD8+ T cells have a tolerance-specific gene profile that can be temporarily overridden under lymphopenic conditions but is inevitably reimposed, which suggests epigenetic regulation. These insights into the regulatory mechanisms that maintain or break self-tolerance may lead to new strategies for the treatment of cancer and autoimmunity.[i]

[i] Schietinger A, Delrow JJ, Basom RS, Blattman JN, Greenberg PD. Rescued tolerant CD8 T cells are preprogrammed to reestablish the tolerant state. Science 2012 Feb 10; 335 (6069): 723-7. Epub 2012 Jan 19. (PMID: 22267581)
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2012
CRI Milestone
CRI RELAUNCHES OPEN ACCESS JOURNAL CANCER IMMUNITY
Details
November 13, 2012
CRI Milestone
CRI RELAUNCHES OPEN ACCESS JOURNAL CANCER IMMUNITY

CI-Logo-Standard_600px-1.jpgCRI relaunches the online, open access journal Cancer Immunity and adopts it as its official journal.

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2012
Major Discovery
ANTI-PD-1 ANTIBODY SHOWS DRAMATIC RESULTS IN PHASE I TRIAL
Details
November 13, 2012
Major Discovery
ANTI-PD-1 ANTIBODY SHOWS DRAMATIC RESULTS IN PHASE I TRIAL

An anti-PD-1 antibody developed by Bristol-Myers Squibb generates excitement with results from a phase I trial showing that, among 236 patients with various types of cancer, the treatment shrank tumors in 28 percent of melanoma patients, 30 percent of patients with kidney cancer, and 18 percent of patients with advanced non-small cell lung cancer.


2012-anti-PD-1-lung-cancer-response.jpg

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2011
Major Discovery
CT10/MAGE-C2 AS INDEPENDENT PREDICTOR OF RECURRENCE IN PROSTATE CANCER
Details
November 13, 2011
Major Discovery
CT10/MAGE-C2 AS INDEPENDENT PREDICTOR OF RECURRENCE IN PROSTATE CANCER
CVC researchers Alex Knuth and Lotta Von Boehmer, and Maries Van Den Broek at the University of Zurich, in collaboration with Lloyd J. Old and Achim Jungbluth at the Ludwig New York Branch, establish CT10/MAGE-C2 as an independent predictor of recurrence in prostate cancer.

von Boehmer L, Keller L, Mortezavi A, Provenzano M, Sais G, Hermanns T, Sulser T, Jungbluth AA, Old LJ, Kristiansen G, van den Broek M, Moch H, Knuth A, Wild PJ. MAGE-C2/CT10 protein expression is an independent predictor of recurrence in prostate cancer. PLoS One 2011; 6: e21366. Epub 2011 Jul 6. (PMID: 21754986)
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2011
Major Discovery
GENE PROFILING STUDY OF CANCER-SPECIFIC CD8+ T CELLS
Details
November 13, 2011
Major Discovery
GENE PROFILING STUDY OF CANCER-SPECIFIC CD8+ T CELLS
Daniel E. Speiser and other CVC investigators perform the first gene profiling study of cancer-specific CD8+ T cells, and demonstrate that lymphocyte dysfunction in cancer tissue is due to multiple molecular alterations, similar as in “exhausted” T cells in patients with chronic infection. The data provide novel drug targets, and show that T cell exhaustion is reversible and limited to anatomical sites of disease.

Baitsch L, Baumgaertner P, Devevre E, Raghav SK, Legat A, Barba L, Wieckowski S, Bouzourene H, Deplancke B, Romero P, Rufer N, Speiser DE. Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients. J Clin Invest 2011 Jun 1; 121: 2350-2360. (PMID: 21555851)
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2011
Major Discovery
ARTIFICIAL ANTIGEN PRESENTING CELLS CAN ENHANCE ADOPTIVE THERAPY
Details
November 13, 2011
Major Discovery
ARTIFICIAL ANTIGEN PRESENTING CELLS CAN ENHANCE ADOPTIVE THERAPY
CVC researchers Lee M. Nadler, Naoto Hirano, Marcus O. Butler, and colleagues report that a new technology using artificial antigen presenting cells (aAPC) could successfully enhance adoptive therapy of tumor antigen-specific CD8+ T cells. In a study involving nine patients with advanced melanoma, the aAPC technology could induce long-term increases in tumor-specific CD8+ T cells, with one patient achieving a complete response and two showing prolonged time to progression.

Butler MO, Friedlander P, Milstein MI, Mooney MM, Metzler G, Murray AP, Tanaka M, Berezovskaya A, Imataki O, Drury L, Brennan L, Flavin M, Neuberg D, Stevenson K, Lawrence D, Hodi FS, Velazquez EF, Jaklitsch MT, Russell SE, Mihm M, Nadler LM, Hirano N. Establishment of antitumor memory in humans using in vitro-educated CD8+ T cells. Sci Transl Med 2011 Apr 27; 3: 80ra34. (PMID: 21525398)
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2011
Field Milestone
27 MEMBER SITES NAMED BY NCI FOR THE CANCER IMMUNOTHERAPY TRIALS NETWORK
Details
November 13, 2011
Field Milestone
27 MEMBER SITES NAMED BY NCI FOR THE CANCER IMMUNOTHERAPY TRIALS NETWORK
NCI names 27 member sites for the Cancer Immunotherapy Trials Network. Site PIs include:
  • Scott J. Antonia, H. Lee Moffitt Cancer Center
  • Nina Bhardwaj, New York University
  • William E. Carson, Ohio State University
  • Laurence J.N. Cooper, The University of Texas MD Anderson Cancer Center
  • Marc Ernstoff, Dartmouth-Hitchcock Norris Cotton Cancer Center
  • Robert Ferris andHassane Zarour, University of Pittsburgh
  • Lawrence Fong, University of California, San Francisco
  • Stephen Hodi, Dana-Farber Cancer Center
  • Thomas Gajewski, University of Chicago
  • Elizabeth Jaffee, Johns Hopkins University School of Medicine
  • Carl June, University of Pennsylvania
  • Howard Kaufman, Rush University Cancer Center
  • Thomas J. Kipps, University of California, San Diego
  • Ronald Levy, Stanford University
  • Kim Lyerly, Duke University Medical Center
  • Jeffrey S. Miller, University of Minnesota
  • Kunle Odunsi, Roswell Park Cancer Institute
  • Pamela Ohashi, University of Toronto Ontario Cancer Instiute
  • Karolina Palucka, Baylor Research Institute and Mount Sinai School of Medicine
  • Joseph D. Rosenblatt, University of Miami
  • Craig Slingluff, University of Virginia
  • Paul M. Sondel, University of Wisconsin
  • Mario Sznol, Yale University
  • John A. Thompson, Fred Hutchinson Cancer Research Center
  • Pierre Triozzi, Case Western Reserve University
  • Walter J. Urba, Providence Cancer Center
  • Edmund K. Waller, Emory University
  • Jedd D. Wolchok, Memorial Sloan-Kettering Cancer Center
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2011
Field Milestone
HALLMARKS OF CANCER EXPANDED
Details
November 13, 2011
Field Milestone
HALLMARKS OF CANCER EXPANDED

Hallmarks-of-Cancer1.jpgDouglas Hanahan and Robert Weinberg publish an update of their seminal review, Hallmarks of Cancer, adding to the list of cancer characteristics the ability of tumors to evade the immune system and emphasizing immune system-induced inflammation as an enabling characteristic in cancer development. Since the review was first published in 2000, Hallmarks has served as the defining model of cancer.

Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell 2011 Mar 14; 144: 646-674. (PMID: 21376230)

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2011
Treatment Approved
NEW INTERFERON FORMULATION APPROVED FOR MELANOMA
Details
November 13, 2011
Treatment Approved
NEW INTERFERON FORMULATION APPROVED FOR MELANOMA
The FDA approves peginterferon alfa-2b (Sylatron™) for the treatment of melanoma.
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2011
Major Discovery
PEPTIDE VACCINE + IL-2 IMPROVES MELANOMA RESPONSES
Details
November 13, 2011
Major Discovery
PEPTIDE VACCINE + IL-2 IMPROVES MELANOMA RESPONSES

Schwartzentruber-Doug-AdvHC.jpgDouglas J. Schwartzentruber and colleagues at The University of Texas MD Anderson Cancer Center demonstrate that patients with metastatic melanoma receiving high doses of interleukin-2 (IL-2) plus a gp100 peptide vaccine had significant improvement in overall clinical response, providing further validation for vaccine approaches to cancer treatment.



Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, Gailani F, Riley L, Conlon K, Pockaj B, Kendra KL, White RL, Gonzalez R, Kuzel TM, Curti B, Leming PD, Whitman ED, Balkissoon J, Reintgen DS, Kaufman H, Marincola FM, Merino MJ, Rosenberg SA, Choyke P, Vena D, Hwu P. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med 2011 Jun 2; 364: 2119-2127. (PMID: 21631324)

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2011
Field Milestone
FDA ISSUES FINAL CANCER VACCINE DEVELOPMENT GUIDELINES
Details
November 13, 2011
Field Milestone
FDA ISSUES FINAL CANCER VACCINE DEVELOPMENT GUIDELINES

1417-big.jpgThe FDA issues its finalized Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines.

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2011
Treatment Approved
IMMUNOTHERAPY APPROVED FOR ADVANCED MELANOMA
Details
November 13, 2011
Treatment Approved
IMMUNOTHERAPY APPROVED FOR ADVANCED MELANOMA

1-yervoy.jpgFDA approves the anti-CTLA-4 monoclonal antibody ipilimumab (Yervoy) for the treatment of metastatic melanoma. Yervoy is the first drug of any kind ever shown to extend survival in metastatic melanoma.

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2011
Major Discovery
NEW T CELL TREATMENT CURES PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
Details
November 13, 2011
Major Discovery
NEW T CELL TREATMENT CURES PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

carT.jpgUsing a novel technique to genetically modify T cells for adoptive transfer, Carl June, Michael Kalos, David Porter, Bruce Levine, and colleagues at the University of Pennsylvania School of Medicine achieve clinical responses in patients with chronic lymphocytic leukemia, including two complete, durable (one year) clinical responses, accompanied by in vivo expansion and long-term functional persistence of gene-modified cells.



Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 2011 Aug 10; 3: 95ra73. (PMID: 21832238)

Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 2011 Aug 25; 365: 725-33. Epub 2011 Aug 10. (PMID: 21830940)

 

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2011
Treatment Approved
NEW DRUG APPROVED FOR MELANOMA
Details
November 13, 2011
Treatment Approved
NEW DRUG APPROVED FOR MELANOMA

vemurafenib.jpgVemurafenib (Zelboraf®, PLX4032), a targeted cancer drug, extends life in patients with advanced melanoma, and is approved by the FDA.

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2011
Treatment Approved
ANTIBODY-DRUG CONJUGATE APPROVED FOR LYMPHOMA
Details
November 13, 2011
Treatment Approved
ANTIBODY-DRUG CONJUGATE APPROVED FOR LYMPHOMA

2011-Adcetris-diagram.pngBrentuximab vedotin (Adcetris), a drug-linked chimeric mouse/human anti-human CD30 monoclonal antibody to treat Hodgkin lymphoma and anaplastic large cell lymphoma, is approved by the FDA.

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2011
Awards & Honors
NOBEL PRIZE FOR INNATE IMMUNOLOGY
Details
November 13, 2011
Awards & Honors
NOBEL PRIZE FOR INNATE IMMUNOLOGY

2012-12-28-ralph-steinman-dies.jpgThe Nobel Foundation announces Bruce Beutler, Jules Hoffmann, and Ralph Steinman (pictured left) as the recipients of the 2011 Nobel Prize in Physiology or Medicine.

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2011
Major Discovery
NY-ESO-1 T CELLS INDUCE REMISSIONS IN SARCOMA AND MELANOMA
Details
November 12, 2011
Major Discovery
NY-ESO-1 T CELLS INDUCE REMISSIONS IN SARCOMA AND MELANOMA

t-cell-cancer-graphic.jpgSteven A. Rosenberg  and colleagues at the Surgery Branch of the National Cancer Institute demonstrate that adoptive immunotherapy with CD8+ T cells genetically engineering to recognize the NY-ESO-1 antigen could induce significant tumor regressions in patients with metastatic synovial sarcoma and melanoma.

Photo courtesy of rockcellarmagazine.com

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2010
Field Milestone
CANCER IMMUNOTHERAPY TRIALS NETWORK ESTABLISHED
Details
November 13, 2010
Field Milestone
CANCER IMMUNOTHERAPY TRIALS NETWORK ESTABLISHED

2010-Cancer-Immunotherapy-Trials-Network-Established-1.jpgThe National Cancer Institute establishes the Cancer Immunotherapy Trials Network (CITN), to be headquartered at the Fred Hutchinson Cancer Research Center and led by Martin (“Mac”) Cheever.

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2010
Major Discovery
THE FIRST CLEAR BENEFIT OF HERCEPTIN FOR BREAST CANCER OBSERVED
Details
November 13, 2010
Major Discovery
THE FIRST CLEAR BENEFIT OF HERCEPTIN FOR BREAST CANCER OBSERVED

2010-Herceptin-and-Breast-Cancer.jpgThe first clear-cut benefit of Herceptin conjugated with an antimicrotubule agent is seen in patients with ‘naked’ Herceptin-resistant breast tumors.



Krop IE, Beeram M, Modi S, Jones SF, Holden SN, Yu W, Girish S, Tibbitts J, Yi JH, Sliwkowski MX, Jacobson F, Lutzker SG, Burris HA. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. J Clin Oncol 2010 Jun 1; 28: 2698-2704. (PMID: 20421541)

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2010
Treatment Approved
DENOSUMAB APPROVED BY THE FDA
Details
November 13, 2010
Treatment Approved
DENOSUMAB APPROVED BY THE FDA

2010-Yongwon-Choi.jpgDenosumab, a human anti-human RANKL—also known as TRANCE, first identified by CRI Investigator Yongwon Choi—is approved by the FDA to reduce the risk of osteoporosis (Prolia) and for the prevention of skeletal-related events in patients with cancers that have metastasized to the bone (Xgeva).

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2010
Treatment Approved
OFATUMUMAB (ARZERRA) APPROVED TO TREAT CHRONIC LYMPHOCYTIC LEUKEMIA
Details
November 13, 2010
Treatment Approved
OFATUMUMAB (ARZERRA) APPROVED TO TREAT CHRONIC LYMPHOCYTIC LEUKEMIA

2010-chronic-lymphocytic-leukemia.jpgOfatumumab (Arzerra), a human anti-human CD20 monoclonal antibody to treat chronic lymphocytic leukemia, is approved by the FDA.

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2010
Awards & Honors
ELIMINATION OF LEUKEMIA CELLS REPORTED
Details
November 13, 2010
Awards & Honors
ELIMINATION OF LEUKEMIA CELLS REPORTED

2010-Ryuzo-Ueda.jpgRyuzo Ueda and colleagues report elimination of leukemia cells by CCR4 antibody in ATL patients.


Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, Yamaguchi K, Yamada Y, Hanada S, Tamura K, Nakamura S, Inagaki H, Ohshima K, Kiyoi H, Ishida T, Matsushima K, Akinaga S, Ogura M, Tomonaga M, Ueda R. Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol 2010 Mar 20; 28: 1591-1598. (PMID: 20177026)

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2010
Tools & Technologies
FIRST TETRAMERS TO MONITOR CD4+ T CELL RESPONSES
Details
November 13, 2010
Tools & Technologies
FIRST TETRAMERS TO MONITOR CD4+ T CELL RESPONSES

tetramer.gifCancer Vaccine Collaborative researchers Danila Valmori, Maha Ayyoub, Immanuel Luescher, and colleagues develop the first tetramer technology to monitor CD4 T cell responses to cancer vaccination.


Ayyoub M, Dojcinovic D, Pignon P, Raimbaud I, Schmidt J, Luescher I, Valmori D. Monitoring of NY-ESO-1 specific CD4+ T cells using molecularly defined MHC class II/His-tag-peptide tetramers. Proc Natl Acad Sci U S A 2010 Apr 20; 107: 7437-7442. (PMID: 20368442)

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2010
CRI Milestone
CRI LAUNCHES VENTURE PHILANTHROPY FUND
Details
November 13, 2010
CRI Milestone
CRI LAUNCHES VENTURE PHILANTHROPY FUND

cvaf-logo-FINAL-300dpi.jpgCancer Research Institute and the Ludwig Institute for Cancer Research announce the launch of the Cancer Vaccine Acceleration Fund (CVAF), a new model of venture philanthropy to drive academic-industry partnership and speed the development of promising multi-component therapeutic cancer vaccines.

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2010
CRI Milestone
ANTI-GITR ANTIBODY BROUGHT INTO FIRST-IN-HUMAN TRIAL
Details
November 13, 2010
CRI Milestone
ANTI-GITR ANTIBODY BROUGHT INTO FIRST-IN-HUMAN TRIAL

aGITR.jpg
Through the Cancer Vaccine Acceleration Fund, CRI and the Ludwig Institute successfully negotiate a partnership to bring the anti-GITR antibody TRX518 into clinical testing for the first time in a trial designed with significant input from Cancer Vaccine Collaborative (CVC) leadership and conducted within the CVC global network. The agreement includes provisions for follow-on studies incorporating TRX518 into NY-ESO-1-based vaccine constructs.

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2010
CRI Milestone
CRI HOLDS FIRST MEETING ON SCHEDULE AND DOSE IN COMBINATION TREATMENT
Details
November 13, 2010
CRI Milestone
CRI HOLDS FIRST MEETING ON SCHEDULE AND DOSE IN COMBINATION TREATMENT

Banner-CIC.jpgThe CRI Cancer Immunotherapy Consortium hosts its 2011 Colloquium, the first meeting of its kind to focus on Schedule and Dose in Combination Therapy.

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2010
Major Discovery
PD-1 CHECKPOINT BLOCKADE SHOWS PROMISE
Details
November 13, 2010
Major Discovery
PD-1 CHECKPOINT BLOCKADE SHOWS PROMISE

PD-1.jpgA PD-1-specific monocolonal antibody induces frequent tumor regressions in patients with advanced melanoma, renal cancer, lung cancer, and colon cancer with very low rates of toxicity. Response correlates with tumor membrane expression of B7-H129.



Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, Gilson MM, Wang C, Selby M, Taube JM, Anders R, Chen L, Korman AJ, Pardoll DM, Lowy I, Topalian SL. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010 Jul 1; 28: 3167-3175. (PMID: 20516446)

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2010
Treatment Approved
FIRST THERAPEUTIC CANCER VACCINE APPROVED
Details
November 13, 2010
Treatment Approved
FIRST THERAPEUTIC CANCER VACCINE APPROVED

provenge.pngIn April 2010, FDA approves the use of sipuleucel-T (Provenge®) for the treatment of prostate cancer. Sipuleucel-T is the first human cancer treatment vaccine to be approved in the United States. The cancer vaccine is the first to show a survival benefit in a phase III trial, conferring a four-month overall survival advantage in men with advanced castrate-resistant prostate cancer.



Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010 Jul 29; 363: 411-422. (PMID: 20818862)

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2010
Major Discovery
CHECKPOINT BLOCKADE EXTENDS SURVIVAL
Details
November 13, 2010
Major Discovery
CHECKPOINT BLOCKADE EXTENDS SURVIVAL

ipilimumab.jpgA CTLA-4-specific monoclonal antibody, ipilimumab (Yervoy®), is the first agent in history to provide a survival advantage in patients with advanced melanoma in a large randomized phase III trial.



Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010 Aug 19; 363: 711-723. (PMID:20525992)

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2000s
2009
Major Discovery
THERAPEUTIC VACCINE CURES PRECANCEROUS GYNECOLOGICAL DISEASE
Details
November 10, 2009
Major Discovery
THERAPEUTIC VACCINE CURES PRECANCEROUS GYNECOLOGICAL DISEASE
A therapeutic vaccine, developed by Cornelis (Kees) Melief and Sjoerd Van Der Burg at Leiden University Medical Center, demonstrates durable complete responses in some women with HPV-16+ vulvar intraepithelial neoplasias (VINs), a disease that normally has a spontaneous regression rate of less than 2 percent.

Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, Berends-van der Meer DM, Vloon AP, Essahsah F, Fathers LM, Offringa R, Drijfhout JW, Wafelman AR, Oostendorp J, Fleuren GJ, van der Burg SH, Melief CJ. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med 2009 Nov 5; 361: 1838-1847. (PMID: 19890126)
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2009
Treatment Approved
SECOND CERVICAL CANCER VACCINE APPROVED
Details
November 10, 2009
Treatment Approved
SECOND CERVICAL CANCER VACCINE APPROVED
The FDA approves Cervarix, a second vaccine that protects against persistent infection with the two types of HPV that cause approximately 70 percent of all cases of cervical cancer worldwide.
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2009
Major Discovery
TET PROTEINS ALTER GENE EXPRESSION IN STEM CELLS AND CANCER
Details
November 10, 2009
Major Discovery
TET PROTEINS ALTER GENE EXPRESSION IN STEM CELLS AND CANCER
Anjana Rao and colleagues Mamta Tahiliani and L. Aravind discover the enzymatic activity of TET proteins as iron and 2-oxoglutarate-dependent dioxygenases that oxidise 5-methylcytosine in DNA, thus altering gene expression in stem cells, cancers, and the brain among others. Loss-of-function mutations in TET2 are shown to be frequent in myelodysplastic syndromes and myeloproliferative neoplasms including chronic myelomonocytic and acute myeloid lymphomas.
 

Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by the MLL fusion partner, TET1. Science 2009 May 15; 324: 930-935. (PMID: 19372391)

Ko M, Huang Y, Jankowska AM, Pape UJ, Tahiliani M, Bandukwala HS, Ahn J, Lamperti ED, Koh KP, Ganetzky R, Liu XS, Aravind L, Agarwal S, Maciejewski J, Rao A. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 2010 Dec 9; 468: 839-843. (PMID: 21057493)
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2009
CRI Milestone
INITIATIVE TO ESTABLISH T CELL ASSAY REPORTING FRAMEWORK LAUNCHED
Details
November 10, 2009
CRI Milestone
INITIATIVE TO ESTABLISH T CELL ASSAY REPORTING FRAMEWORK LAUNCHED

MIATA_1.jpgA collaborative group including the CRI Cancer Immunotherapy Consortium (CIC), the Association for Cancer Immunotherapy (CIMT) Immunoguiding Program (CIP), and scientists at Stanford University launch the Minimal Information About T cell Assays (MIATA) Project, the first systematic effort to establish a framework for reporting immune monitoring data from T cell assays used in clinical trials, with the goal of fostering reliability of data to facilitate meaningful interpretation, comparison, and meta-analysis across clinical trials.

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2009
Major Discovery
NEW T CELL DIFFERENTIATION PROGRAM IDENTIFIED
Details
November 10, 2009
Major Discovery
NEW T CELL DIFFERENTIATION PROGRAM IDENTIFIED
Chen Dong and two other groups identify the B cell lymphoma 6 protein (BCL6) as a key transcription factor governing the differentiation and function of T follicular helper (Tfh) cells. Tfh cells are known to regulate B cells in the germinal center reactions, in which they increase their antibody affinity and differentiate into memory cells. Germinal center is also a hotbed for many B cell malignancies.

BCL6 is frequently mutated in diffuse large B cell lymphoma, the most common type of lymphoma in adults, accounting for 30% to 40% of all new diagnoses of non-Hodgkin lymphoma, and contributes to the pathogenesis of the disease.

Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S, Matskevitch TD, Wang YH, Dong C. Science 2009 Aug 21; 325: 1001-1005. (PMID: 19628815)
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2009
Major Discovery
FINDINGS ON A MYCOBACTERIAL CELL WALL-DNA COMPLEX
Details
November 10, 2009
Major Discovery
FINDINGS ON A MYCOBACTERIAL CELL WALL-DNA COMPLEX

2008-Alvaro-Morales.jpgAlvaro Morales reports the results of a multicenter study on the efficacy of a mycobacterial cell wall-DNA complex in patients with non-muscle invasive bladder cancer refractory to standard intravesical therapies.



Morales A, Phadke K, Steinhoff G. Intravesical mycobacterial cell wall-DNA complex in the treatment of carcinoma in situ of the bladder after standard intravesical therapy has failed. J Urol 2009 Mar; 181:1040-1044. (PMID: 19150551)

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2009
Major Discovery
DISCOVERIES ON NUCLEOSOMES
Details
November 10, 2009
Major Discovery
DISCOVERIES ON NUCLEOSOMES

2009-Nucleosomes.jpgHong Ming Shen, Ursula Storb, and colleagues show that nucleosomes inhibit access of the cytidine deaminase AID to DNA, unless the DNA is transcribed.
 



Shen HM, Poirier MG, Allen M, North J, Lal R, Widom J, Storb U. The activation induced cytidine deaminase (AID) efficiently targets DNA in nucleosomes, but only during transcription. J Exp Med 2009; 206: 1057-1071. (PMID: 19380635)

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2009
Major Discovery
IDENTIFICATION OF A NEW NY-ESO-1 EPITOPE
Details
November 10, 2009
Major Discovery
IDENTIFICATION OF A NEW NY-ESO-1 EPITOPE

2009-Danila-Valmori.jpgCVC researchers Danila Valmori and Maha Ayyoub identify a new NY-ESO-1 epitope, 119-143 (core region 123-137), presented by HLA-DR52b (HLA-DRB3*0202), an MHC class II allele expressed by half of Caucasians, that is immunodominant in the context of vaccine-elicited immune responses. This finding is instrumental for the immunologic monitoring of vaccination trials targeting the NY-ESO-1 tumor antigen.



Bioley G, Dousset C, Yeh A, Dupont B, Bhardwaj N, Mears G, Old LJ, Ayyoub M, Valmori D. Vaccination with recombinant NY-ESO-1 protein elicits immunodominant HLA-DR52b-restricted CD4+ T cell responses with a conserved T cell receptor repertoire. Clin Cancer Res 2009 Jul 1; 15: 4467-4474. (PMID: 19531622)

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2008
Treatment Approved
FIRST APPROVAL IN WORLD OF THERAPEUTIC VACCINE FOR CANCER
Details
November 10, 2008
Treatment Approved
FIRST APPROVAL IN WORLD OF THERAPEUTIC VACCINE FOR CANCER

Pramod-Srivastava.jpgOncophage, the therapeutic vaccine for kidney cancer developed by Pramod Srivastava, is approved in Russia, making it the first therapeutic vaccine worldwide to be approved for patients.



Wood CG, Srivastava PK, Lacombe L, Wentworth K, Yuh L, Gupta R, Figlin R, Flanigan R, Escudier B. A randomized Phase 3 trial comparing adjuvant therapy with autologous tumor-derived heat shock protein gp96 (vitespen) vs. observation in patients at high risk of recurrence of renal cell carcinoma. Lancet 2008 Jul 12; 372: 145-154. (PMID: 18602688)

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2008
Tools & Technologies
NEW BISPECIFIC ANTIBODY TECHNOLOGY DEVELOPED
Details
November 10, 2008
Tools & Technologies
NEW BISPECIFIC ANTIBODY TECHNOLOGY DEVELOPED
Micromet develops a recombinant antibody fragment that is bispecific, designed to target the CD19 antigen on B cell lymphoma and the CD3 antigen on T cells, effectively using the T cells to kill the lymphoma cells. The technology is name BiTE, for Bispecific T cell Engager.

Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, Noppeney R, Viardot A, Hess G, Schuler M, Einsele H, Brandl C, Wolf A, Kirchinger P, Klappers P, Schmidt M, Riethmüller G, Reinhardt C, Baeuerle PA, Kufer P. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 2008 Aug 15; 321: 974-977. (PMID: 18703743)
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2008
Major Discovery
GENETICALLY ENGINEERED T CELLS TREAT B CELL LYMPHOMAS
Details
November 10, 2008
Major Discovery
GENETICALLY ENGINEERED T CELLS TREAT B CELL LYMPHOMAS
Stanley Riddell and Philip Greenberg at the Fred Hutchinson Cancer Research Center, Michael Jensen at City of Hope National Medical Center and Beckman Research Institute, and others at the University of Washington report on a clinical trial showing that T cells engineered to express chimeric antigen receptors induce clinical responses in patients with B cell lymphomas.

Till B, Jensen MC, Wang J, Chen EY, Wood BL, Greisman HA, Qian X, James SE, Raubitschek A, Forman SJ, Gopal AK, Pagel JM, Lindgren CG, Greenberg PD, Riddell SR, Press OW. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood 2008 Sep 15; 112: 2261-2271. (PMID: 18509084)
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2008
Major Discovery
GENETICALLY ENGINEERED T CELLS TREAT B CELL LYMPHOMAS
Details
November 10, 2008
Major Discovery
GENETICALLY ENGINEERED T CELLS TREAT B CELL LYMPHOMAS
Stanley Riddell and Philip Greenberg at the Fred Hutchinson Cancer Research Center, Michael Jensen at City of Hope National Medical Center and Beckman Research Institute, and others at the University of Washington report on a clinical trial showing that T cells engineered to express chimeric antigen receptors induce clinical responses in patients with B cell lymphomas.

Till B, Jensen MC, Wang J, Chen EY, Wood BL, Greisman HA, Qian X, James SE, Raubitschek A, Forman SJ, Gopal AK, Pagel JM, Lindgren CG, Greenberg PD, Riddell SR, Press OW. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood 2008 Sep 15; 112: 2261-2271. (PMID: 18509084)
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2008
CRI Milestone
CRI ASSUMES CANCER VACCINE CONSORTIUM
Details
November 10, 2008
CRI Milestone
CRI ASSUMES CANCER VACCINE CONSORTIUM

2008-Cancer-Immunotherapy-Consortium.jpgCancer Research Institute assumes Cancer Vaccine Consortium (now Cancer Immunotherapy Consortium) from the Sabin Vaccine Institute.

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2007
Major Discovery
CANCER-IMMUNE EQUILIBRIUM DEMONSTRATED
Details
November 10, 2007
Major Discovery
CANCER-IMMUNE EQUILIBRIUM DEMONSTRATED
An international research effort led by Lloyd J. Old, Robert Schreiber, and Mark Smyth provides the first demonstration of cancer-immune equilibrium.

“The Cancer Research Institute has been the fundamental body that has globally underpinned the whole discipline of cancer immunology. In Australia we have benefited from their graduate teaching program. It has funded a whole generation of Australia's next research leaders in cancer immunology.” – Mark J. Smyth
 

Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ, Smyth MJ, Schreiber RD. Adaptive immunity maintains occult cancer in an equilibrium state. Nature 2007 Dec 6; 450: 903-907. (PMID: 18026089)
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2007
Tools & Technologies
NEW IMMUNE PARAMETERS FOR CANCER PROGNOSIS
Details
November 10, 2007
Tools & Technologies
NEW IMMUNE PARAMETERS FOR CANCER PROGNOSIS
Jérôme Galon and Wolf Hervé Fridman introduce the concept of “immune contexture”—associating the nature, the density, the functional orientation, and the location of immune cells within the tumor—to define the prognosis of cancer patients.

Galon J, Fridman WH, Pages F. The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res 2007 Mar 1; 67: 1883-1886. (PMID: 17332313)
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2007
Major Discovery
DISCOVERIES ON CTLA-4-SPECIFIC ANTIBODIES
Details
November 10, 2007
Major Discovery
DISCOVERIES ON CTLA-4-SPECIFIC ANTIBODIES

2007-prostate-cancer.jpgCTLA-4-specific antibodies are shown to induce tumor responses in renal and prostate cancers.
 



Small EJ, Sacks N, Nemunaitis J, Urba WJ, Dula E, Centeno AS, Nelson WG, Ando D, Howard C, Borellini F, Nguyen M, Hege K, Simons JW. Granulocyte macrophage colony-stimulating factor--secreting allogeneic cellular immunotherapy for hormone-refractory prostate cancer. Clin Cancer Res 2007 Jul 1; 13: 3883-3891. (PMID: 17606721) Download PDF

Yang JC, Hughes M, Kammula U, Royal R, Sherry RM, Topalian SL, Suri KB, Levy C, Allen T, Mavroukakis S, Lowy I, White DE, Rosenberg SA. Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J Immunother 2007 Nov-Dec; 30: 825-830. (PMID: 18049334 ) Download PDF

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2007
Major Discovery
IDENTIFICATION OF A NOVEL MECHANISM OF T CELL HOMEOSTASIS
Details
November 10, 2007
Major Discovery
IDENTIFICATION OF A NOVEL MECHANISM OF T CELL HOMEOSTASIS

2007-T-cell.jpgCRI Investigator Gabriel Rabinovich and his team identify a novel mechanism of T cell homeostasis based on differential glycosylation of T helper cell subsets.



Toscano MA, Bianco GA, Ilarregui JM, Croci DO, Correale J, Hernandez JD, Zwirner NW, Poirier F, Riley EM, Baum LG, Rabinovich GA. Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nature Immunol 2007 Aug; 8: 825-834. (PMID: 17589510)

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2007
Major Discovery
FINDINGS FROM THE FIRST NEOADJUVANT TRIAL OF INTERFERON
Details
November 10, 2007
Major Discovery
FINDINGS FROM THE FIRST NEOADJUVANT TRIAL OF INTERFERON
The first neoadjuvant trial of interferon (UPCI 00-008) reveals its effects are immunological, and mediated through modulation of STAT3 and dendritic cells, as well as T cell responses to melanoma.
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2007
Treatment Approved
CONDITIONAL APPROVAL FOR A THERAPEUTIC VACCINE TO TREAT LATE-STAGE MELANOMA IN DOGS
Details
November 10, 2007
Treatment Approved
CONDITIONAL APPROVAL FOR A THERAPEUTIC VACCINE TO TREAT LATE-STAGE MELANOMA IN DOGS

2007-Jedd-D-Wolchok.jpgA therapeutic vaccine to treat dogs with late-stage melanoma, created by Jedd D. Wolchok, receives conditional approval from the United States Department of Agriculture. 


3/26/2007

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2007
Awards & Honors
CRI'S 2007 COLEY AWARD GOES TO FC RECEPTORS RESEARCHER
Details
November 10, 2007
Awards & Honors
CRI'S 2007 COLEY AWARD GOES TO FC RECEPTORS RESEARCHER

2007-Jeffrey-V-Ravetch.jpgCRI presents the Coley Award to Jeffrey V. Ravetch for his work on Fc receptors, leading to fundamental discoveries critical to improving the design of therapeutic antibodies.

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2007
CRI Milestone
MERGER OF CRI AND IRVINGTON INSTITUTE FOR IMMUNOLOGICAL RESEARCH
Details
November 10, 2007
CRI Milestone
MERGER OF CRI AND IRVINGTON INSTITUTE FOR IMMUNOLOGICAL RESEARCH
Cancer Research Institute and Irvington Institute for Immunological Research merge. CRI assumes leadership of combined organization and renames its fellowship program the Irvington Postdoctoral Fellowship Program of the Cancer Research Institute.
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2006
Treatment Approved
FIRST FULLY HUMAN MONOCLONAL ANTIBODY FOR CANCER APPROVED
Details
November 10, 2006
Treatment Approved
FIRST FULLY HUMAN MONOCLONAL ANTIBODY FOR CANCER APPROVED
Panitumumab (Vectibix), a human anti-human EGFR monoclonal antibody to treat metastatic colorectal cancer, is approved by the FDA. Generated from transgenic mice with human immunoglobulin genes, panitumumab is also the first fully human monoclonal antibody approved for cancer therapy.
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2006
Major Discovery
CCL3/CCL4 CHEMOKINES ENHANCE IMMUNE CELL COOPERATION AND HELP
Details
November 10, 2006
Major Discovery
CCL3/CCL4 CHEMOKINES ENHANCE IMMUNE CELL COOPERATION AND HELP
Alex Huang and Ronald Germain, in the Laboratory of Immunology, NIAID/NIH, show the role of inflammatory chemokines CCL3/CCL4 in enhancing CD8/CD4/DC cooperation and T cell help.
Castellino F, Huang AY, Altan-Bonnet G, Stoll S, Scheinecker C, Germain RN. Chemokines enhance immunity by guiding naïve CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction. Nature 2006 Apr 13; 440: 890-895. (PMID: 16612374)
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2006
Major Discovery
RESEARCHERS SHOW VACCINATION CAN WORSEN TUMOR ANTIGEN TOLERANCE
Details
November 10, 2006
Major Discovery
RESEARCHERS SHOW VACCINATION CAN WORSEN TUMOR ANTIGEN TOLERANCE
Gang Zhou, Charles G. Drake, and Hyam I. Levitsky demonstrate that therapeutic cancer vaccination can expand tumor-specific regulatory T cells that inhibit the expansion of naïve tumor-specific T cells and block the execution of expanded effector cell populations, suggesting that vaccination can actually worsen tolerance to tumor antigens.
 

Zhou G, Drake CG, Levitsky HI. Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood 2006 Jan 15; 107: 628-636. (PMID: 16179369)
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2006
Tools & Technologies
NEW ADOPTIVE T CELL TECHNOLOGY
Details
November 10, 2006
Tools & Technologies
NEW ADOPTIVE T CELL TECHNOLOGY
Steven A. Rosenberg and colleagues, including Mark Dudley, show that T cells genetically engineered to express T cell receptor genes can be used to treat patients with melanoma, bypassing the need to expand tumor-specific T cells from patients with cancer.
 

Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006 Oct 6; 314: 126-129. (PMID: 16946036)
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2006
Treatment Approved
PREVENTIVE VACCINE FOR CERVICAL CANCER APPROVED
Details
November 10, 2006
Treatment Approved
PREVENTIVE VACCINE FOR CERVICAL CANCER APPROVED
FDA approves the “cervical cancer vaccine” Gardasil, which protects against two types of HPV that cause approximately 70 percent of all cases of cervical cancer worldwide. Gardasil was made possible by technology developed by CRI-funded scientist Ian H. Frazer.

“This new vaccine that prevents cervical cancer grew out of research funded by CRI.” – Ian Frazer, 2003 CRI Annual Report
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2006
Major Discovery
DISCOVERIES ON ORAI1
Details
November 10, 2006
Major Discovery
DISCOVERIES ON ORAI1
Anjana Rao and colleagues Patrick Hogan, Stefan Feske, and Yousang Gwack use an RNAi screen in Drosophila cells to identify ORAI1 as the elusive pore subunit of the CRAC store-operated calcium entry channel in non-excitable cells, and show that a mutation in ORAI1 is responsible for a severe hereditary primary immunodeficiency syndrome.
 

Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel S-H, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A. A mutation in Orai1 causes immune deficiency by abrogating store-operated Ca2+ entry and CRAC channel function. Nature 2006 May 11; 441: 179-185. (PMID: 16582901)

Prakriya M, Feske S, Gwack Y, Srikanth S, Rao A, Hogan PG. Orai1 is an essential pore subunit subunit of the CRAC channel. Nature 2006 Sep 14; 443: 230-233. (PMID: 16921383)
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2006
Major Discovery
CVC RESEARCHERS REPORT ON THE FIRST CLINICAL TRIAL WITH VIRUS-ENCODED NY-ESO-1
Details
November 10, 2006
Major Discovery
CVC RESEARCHERS REPORT ON THE FIRST CLINICAL TRIAL WITH VIRUS-ENCODED NY-ESO-1

2006-NY-ESO-1.jpgCVC researchers, including Elke Jaeger, Julia Karbach, Danila Valmori, Maha Ayyoub, Gerd Ritter, Dirk Jaeger, Eric Hoffman, Linda Pan, Lloyd J. Old, and Alex Knuth report on the first clinical trial with virus-encoded NY-ESO-1 in a prime-boost setting.



Jäger E, Karbach J, Gnjatic S, Neumann A, Bender A, Valmori D, Ayyoub M, Ritter E, Ritter G, Jäger D, Panicali D, Hoffman E, Pan L, Oettgen H, Old LJ, Knuth A. Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients. Proc Natl Acad Sci U S A 2006 Sep 26; 103: 14453-14458. (PMID: 16984998) Download PDF

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2006
Major Discovery
THE FIRST DEMONSTRATION TO SHOW THE FUNCTION OF A SYNTHETIC VACCINE IN HUMANS
Details
November 10, 2006
Major Discovery
THE FIRST DEMONSTRATION TO SHOW THE FUNCTION OF A SYNTHETIC VACCINE IN HUMANS

2006-Daniel-Speiser.jpgDaniel Speiser, Pedro Romero, and colleauges report the first demonstration in humans that a synthetic vaccine can rapidly elicit strong specific CD8+ T cell responses in a majority of patients.
 



Speiser DE, Liénard D, Rufer N, Rubio-Godoy V, Rimoldi D, Lejeune F, Krieg AM, Cerottini JC, Romero P. Rapid and strong CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J Clin Invest 2005 Mar; 115: 739-746. (PMID: 15696196) Download PDF

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2006
Treatment Approved
TRASTUZUMAB (HERCEPTIN) APPROVED TO TREAT BREAST CANCER
Details
November 10, 2006
Treatment Approved
TRASTUZUMAB (HERCEPTIN) APPROVED TO TREAT BREAST CANCER

2006-trastuzumab-(Herceptin).jpgFDA approves trastuzumab (Herceptin) for use with other drugs in the adjuvant treatment of women with early-stage node-positive HER2-overexpressing breast cancer.

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2006
Treatment Approved
DRUGS APPROVED TO TREAT MULTIPLE MYELOMA
Details
November 10, 2006
Treatment Approved
DRUGS APPROVED TO TREAT MULTIPLE MYELOMA
FDA approves the drugs thalidomide and lenalidomide, a thalidomide derivative, for the treatment of patients with multiple myeloma.
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2006
Major Discovery
BULK T CELLS TRANSDUCED WITH T CELL RECEPTOR GENES USED TO TREAT PATIENTS WITH MELANOMA
Details
November 10, 2006
Major Discovery
BULK T CELLS TRANSDUCED WITH T CELL RECEPTOR GENES USED TO TREAT PATIENTS WITH MELANOMA

2006-Steven-A-Rosenberg.jpgSteven A. Rosenberg and colleagues show that bulk T cells transduced with T cell receptor genes are used to treat patients with melanoma, bypassing the need to expand tumor-specific T cells from patients with cancer.
 



Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006 Oct 6; 314: 126-129. (PMID: 16946036) Download PDF

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2006
Awards & Honors
CRI'S 2006 COLEY AWARD
Details
November 10, 2006
Awards & Honors
CRI'S 2006 COLEY AWARD
CRI presents the Coley Award to Shizuo Akira, Bruce A. Beutler, Ian H. Frazer, and Harald zur Hausen.
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2005
Major Discovery
NEW BREAST CANCER VACCINE STRATEGY DEVELOPED
Details
November 10, 2005
Major Discovery
NEW BREAST CANCER VACCINE STRATEGY DEVELOPED
Reshma Singh, in the laboratory of Yvonne Paterson, reports success with a novel breast cancer vaccine tested in mice utilizing Listeria monocytogenes bacteria that have been genetically engineered to produce HER-2/neu antigen, which is overexpressed in breast, ovarian, lung, pancreatic, and gastrointestinal cancers. Their bacteria-based vaccine is shown to stimulate immune responses specific to a broader number of HER-2/neu antigen epitopes than previously achieved, and result in controlled tumor growth.

Singh R, Dominiecki ME, Jaffee EM, Paterson Y. Fusion to Listeriolysin O and delivery by Listeria monocytogenes enhances the immunogenicity of HER-2/neu and reveals subdominant epitopes in the FVB/N mouse. J Immunol 2005 Sep 15; 175: 3663-3673. (PMID: 16148111)
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2005
Major Discovery
NEW T CELL SUBTYPE IDENTIFIED
Details
November 10, 2005
Major Discovery
NEW T CELL SUBTYPE IDENTIFIED
Chen Dong and Casey Weaver independently identify IL-17-producing CD4+ T cells as the third lineage of helper T cells, which were termed as T helper 17 (Th17). Th17 cells have since been shown to be critical in inflammatory diseases and cancer.
 

Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005 Nov; 6: 1133-1141. (PMID:16200068)

Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 2005 Nov; 6: 1123-1132. (PMID:16200070)
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2005
Major Discovery
DISCOVERIES ABOUT DNA DAMAGE RESPONSE
Details
November 10, 2005
Major Discovery
DISCOVERIES ABOUT DNA DAMAGE RESPONSE
David Raulet and colleagues show that the DNA damage response, a kinase cascade induced in early stage cancer cells, induces tumor cells to display ligands that activate natural killer cells and induce tumor cell killing.
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2005
Major Discovery
DISCOVERIES ON POST-VACCINATION MELANOMA REGRESSION
Details
November 10, 2005
Major Discovery
DISCOVERIES ON POST-VACCINATION MELANOMA REGRESSION

2005-Pierre-Coulie.jpgChristophe Lurquin, Thierry Boon, and Pierre Coulie show that post-vaccination melanoma regression involves tumor-specific T cells, some of which being already present before vaccination, that recognize antigens different than those of the vaccine. It suggests that immunosuppression prevails in tumors prior to vaccination.
 



Germeau C, Ma W, Schiavetti F, Lurquin C, Henry E, Vigneron N, Brasseur F, Lethé B, De Plaen E, Velu T, Coulie PG. High frequency of anti-tumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens. J Exp Med 2005 Jan 17; 201: 241-248. (PMID: 15657293) Download PDF

Lurquin C, Lethé B, Corbière V, Théate I, van Baren N, Coulie PG, Boon T. Contrasting frequencies of anti-tumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen. J Exp Med 2005 Jan 17; 201: 249-257. (PMID: 15657294) Download PDF

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2005
CRI Milestone
CRI'S PROVIDES SEED FUNDING FOR IMMUNOTHERAPY FOR A PHASE 1B TRIAL OF VIRUS
Details
November 10, 2005
CRI Milestone
CRI'S PROVIDES SEED FUNDING FOR IMMUNOTHERAPY FOR A PHASE 1B TRIAL OF VIRUS
CRI provides seed funding to Ian Frazer for “A phase 1b trial of virus like particle immunotherapy for HPV associated infection.” These studies would lead to the development of Gardasil and other preventive vaccines for cervical cancer.
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2005
Major Discovery
DISCOVERIES ON HUMAN CANCER-SPECIFIC CYTOTOXIC CD8 T CELLS
Details
November 10, 2005
Major Discovery
DISCOVERIES ON HUMAN CANCER-SPECIFIC CYTOTOXIC CD8 T CELLS

2005-Daniel-E-Speiser.jpgDaniel E. Speiser and coworkers demonstrate that human cancer-specific cytotoxic CD8 T cells are strongly activated after vaccination with peptides and CpG oligonucleotides, representing the currently most powerful synthetic cancer vaccine formulation.[i] Consequently, circulating cancer-specific T-cells become highly functional in vivo, which correlates with disease-free survival of melanoma patients.[ii]
 



[i] Speiser DE. Lienard D, Rufer N, Rubio-Godoy V, Rimoldi D, Lejeune F, Krieg AM, Cerottini JC, Romero P. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J Clin Invest 2005 Mar; 115: 739-746. (PMID: 15696196) Download PDF

[ii] Baumgaertner P, Jandus C, Rivals JP, Derre L, Lovgren T, Baitsch L, Guillaume P, Luescher IF, Berthod G, Matter M, Rufer N, Michielin O, Speiser DE. Vaccination-induced functional competence of circulating human tumor-specific CD8 T-cells. Int J Cancer 2011 Jul 27. (PMID: 21796616)

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2005
Major Discovery
DISCOVERIES ON TCR SIGNALING MICROCLUSTERS
Details
November 10, 2005
Major Discovery
DISCOVERIES ON TCR SIGNALING MICROCLUSTERS

2005-Michael-Dustin.jpgMichael Dustin and Takashi Saito demonstrate TCR signaling microclusters with natural ligands and establish their relationship to supramolecular activation clusters (SMACs).



Campi G, Varma R, Dustin ML. Actin and agonist MHC-peptide complex-dependent T cell receptor microclusters as scaffolds for signaling. J Exp Med 2005 Oct 17; 202: 1031-1036. (PMID: 16216891) Download PDF

Varma R, Campi G, Yokosuka T, Saito T, Dustin ML. T cell receptor-proximal signals are sustained in peripheral microclusters and terminated in the central supramolecular activation cluster. Immunity 2006 Jul; 25: 117-127. (PMID: 16860761) Download PDF

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2005
Major Discovery
MECHANISM REVERSING IMMUNE SUPPRESSION FIRST DESCRIBED
Details
November 10, 2005
Major Discovery
MECHANISM REVERSING IMMUNE SUPPRESSION FIRST DESCRIBED

2005-Rong-Fu-Wang.JPGRong-Fu Wang and colleagues are the first to describe a mechanism that can reverse immune suppression by regulatory T cells, mediated through Toll-like receptor 8.
 



Peng G, Guo Z, Kiniwa Y, Voo KS, Peng W, Fu T, Wang DY, Li Y, Wang HY, Wang RF. Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function. Science 2005 Aug 26; 309: 1380-1384. (PMID: 16123302)

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2005
Treatment Approved
DRUG APPROVED TO TREAT BREAST CANCER
Details
November 10, 2005
Treatment Approved
DRUG APPROVED TO TREAT BREAST CANCER
FDA approves the aromatase inhibitors anastrozole and exemestane for the adjuvant treatment of hormone receptor-positive early-stage breast cancer.
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2005
Treatment Approved
DRUG APPROVED TO TREAT BREAST CANCER
Details
November 10, 2005
Treatment Approved
DRUG APPROVED TO TREAT BREAST CANCER
FDA approves the aromatase inhibitors anastrozole and exemestane for the adjuvant treatment of hormone receptor-positive early-stage breast cancer.
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2005
Awards & Honors
CRI'S 2005 COLEY AWARD
Details
November 10, 2005
Awards & Honors
CRI'S 2005 COLEY AWARD

2005-James-P-Allison.jpgCRI presents the Coley Award to James P. Allison.

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2005
Major Discovery
A BETTER PREDICTOR OF PATIENT SURVIVAL FOUND
Details
November 10, 2005
Major Discovery
A BETTER PREDICTOR OF PATIENT SURVIVAL FOUND

2005-Wolf-Herve-Fridman.jpgWolf Hervé Fridman and Jérôme Galon report in the New England Journal of Medicine and Science providing quantitative insights into the immune variables involved in the clinical course and prognosis in colorectal cancer and demonstrating that the type, density, and location of immune cells within tumor samples were found to be a better predictor of patient survival than previous pathological criteria for tumor staging.
 



Pagès F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugenc P-H, Trajanoski Z, Fridman W-H, Galon J. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 2005 Dec 22; 353: 2654. (PMID: 16371631)

Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, Tosolini M, Camus M, Berger A, Wind P, Zinzingohoué, Bruneval P, Cugenc P-H, Trajanoski Z, Fridman W-H, Pagès. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006 Sep 29; 313: 1960-1964. (PMID: 17008531)

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2004
Treatment Approved
LETROZOLE APPROVED TO TREAT EARLY-STAGE BREAST CANCER
Details
November 10, 2004
Treatment Approved
LETROZOLE APPROVED TO TREAT EARLY-STAGE BREAST CANCER

2003-breast-cancer.jpgLetrozole is approved by the FDA for the adjuvant treatment of early-stage breast cancer in postmenopausal women who have already been treated with 5 years of tamoxifen therapy.

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2004
Major Discovery
THE FIRST TUMOR ANTIGENIC PEPTIDES PRODUCED BY PEPTIDE SPLICING REPORTED
Details
November 10, 2004
Major Discovery
THE FIRST TUMOR ANTIGENIC PEPTIDES PRODUCED BY PEPTIDE SPLICING REPORTED

2004-James-C-Yang.jpgThe first tumor antigenic peptides produced by peptide splicing are reported by Ken-Ichi Hanada and James C. Yang[i] and by Nathalie Vigneron and Benoit Van den Eynde.[ii] The latter authors further show that peptide splicing occurs in the proteasome by transpeptidation.


[i] Hanada K, Yewdell JW, Yang JC. Immune recognition of a human renal cancer antigen through post-translational protein splicing. Nature 2004 Jan 15; 427: 252-256. (PMID: 14724640)

[ii] Vigneron N, Stroobant V, Chapiro J, Ooms A, Degiovanni G, Morel S, van der Bruggen P, Boon T, Van den Eynde B. An antigenic peptide produced by peptide splicing in the proteasome. Science 2004 Apr 23; 304: 587-590. (PMID: 15001714)

Warren EH, Vigneron NJ, Gavin MA, Coulie PG, Stroobant V, Dalet A, Tykodi SS, Xuereb SM, Mito JK, Riddell SR, Van den Eynde BJ. An antigen produced by splicing of noncontiguous peptides in the reverse order. Science 2006 Sep 8; 313: 1444-1447. (PMID: 16960008)

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2004
Major Discovery
IDENTIFICATION OF A NOVEL STRATEGY MEDIATED BY SECRETION OF THE SUGAR-BINDING PROTEIN GALECTIN-1
Details
November 10, 2004
Major Discovery
IDENTIFICATION OF A NOVEL STRATEGY MEDIATED BY SECRETION OF THE SUGAR-BINDING PROTEIN GALECTIN-1

2004-Gabriel-Rabinovich.JPGCRI Investigator Gabriel Rabinovich and his team identify a novel strategy mediated by secretion of the sugar-binding protein galectin-1 that is used by tumors to escape the immune response.

“As a recipient of a CRI Investigator Research Award and a scientist working in South America, I have to say that receiving a grant from the CRI was the best experience at the begining of my scientific career in Tumor Immunology.” – Gabriel Rabinovich
 



Rubinstein N, Alvarez M, Zwirner NW, Toscano MA, Ilarregui JM, Bravo A, Mordoh J, Fainboim L, Podhajcer OL, Rabinovich GA. Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; A potential mechanism of tumor-immune privilege. Cancer Cell 2004 Mar; 5: 241-251. (PMID: 15050916)

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2004
Major Discovery
DEMONSTRATION OF IMMUNE RESPONSE INDUCED BY VACCINATION IN A CVC PHASE 1 CLINICAL TRIAL
Details
November 10, 2004
Major Discovery
DEMONSTRATION OF IMMUNE RESPONSE INDUCED BY VACCINATION IN A CVC PHASE 1 CLINICAL TRIAL

2004-vaccination.jpgA Cancer Vaccine Collaborative (CVC) phase 1 clinical trial at the Weill Medical College of Cornell University successfully demonstrates that vaccination with a cancer-specific recombinant protein antigen can successfully induce a fully integrated immune response in humans, consisting of antibody, CD4+ T cell, and CD8+ T cell responses. In the trial, patients with non-small cell lung cancer were treated with a vaccine consisting of the cancer antigen MAGE-3 and GlaxoSmithKline’s immunological adjuvant AS02B. The study found that vaccine injection induced a MAGE-3 specific T cell and antibody response.


Atanackovic D, Altorki NK, Stockert E, Williamson B, Jungbluth AA, Ritter E, Santiago D, Ferrara CA, Matsuo M, Selvakumar A, Dupont B, Chen Y-T, Hoffman EW, Ritter G, Old LJ, Gnjatic S. Vaccine-induced CD4+ T cell responses to MAGE-3 protein in lung cancer patients. J Immunol 2004 Mar 1; 172: 3289-3296. (PMID: 14978137) Download PDF

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2004
Treatment Approved
BEVACIZUMAB (AVASTIN) APPROVED TO TREAT METASTATIC COLORECTAL CANCER
Details
November 10, 2004
Treatment Approved
BEVACIZUMAB (AVASTIN) APPROVED TO TREAT METASTATIC COLORECTAL CANCER

2004-metastatic-colorectal-cancer.jpgThe monoclonal antibody bevacizumab (Avastin) is approved by the FDA for use with other drugs in the treatment of metastatic colorectal cancer. Bevacizumab blocks the activity of vascular endothelial growth factor (VEGF), which stimulates angiogenesis.

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2004
Treatment Approved
CETUXIMAB (ERBITUX) APPROVED TO TREAT METASTATIC COLORECTAL CANCER
Details
November 10, 2004
Treatment Approved
CETUXIMAB (ERBITUX) APPROVED TO TREAT METASTATIC COLORECTAL CANCER

2004-cetuximab-(Erbitux).jpgThe monoclonal antibody cetuximab (Erbitux) is approved by the FDA for the treatment of metastatic colorectal cancer. Cetuximab inhibits the activity of a protein called epidermal growth factor receptor (EGFR), which is overexpressed in some cancers.

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2004
Treatment Approved
OXALIPLATIN APPROVED TO TREAT COLORECTAL CANCER
Details
November 10, 2004
Treatment Approved
OXALIPLATIN APPROVED TO TREAT COLORECTAL CANCER
The FDA approves oxaliplatin, a platinum-containing drug, for use in the treatment of advanced colorectal cancer.
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2004
Awards & Honors
CRI'S 2004 COLEY AWARD FOR CONTRIBUTION IN THE FIELD OF REGULATORY T CELLS
Details
November 10, 2004
Awards & Honors
CRI'S 2004 COLEY AWARD FOR CONTRIBUTION IN THE FIELD OF REGULATORY T CELLS

2004-Ethan-M-Shevach.jpgCRI presents the Coley Award to Shimon Sakaguchi and Ethan M. Shevach for their contributions to the understanding of regulatory T cells.

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2003
Major Discovery
DISCOVERIES ON ANTIGEN-SPECIFIC CD4 AND CD8 T CELL
Details
November 13, 2003
Major Discovery
DISCOVERIES ON ANTIGEN-SPECIFIC CD4 AND CD8 T CELL

2003-invariant-natural-killer-T-(iNKT)-cell-(1).jpgVincenzo Cerundolo and colleagues demonstrate that co-injection of invariant natural killer T (iNKT) cell agonists together with antigenic proteins enhances antigen-specific CD4 and CD8 T cell responses. This concept has been tested in the clinic to jump-start antigen-specific T and B cell responses.
 



Hermans IF, Silk JD, Gileadi U, Salio M, Mathew B, Ritter G, Schmidt R, Harris AL, Old LJ, Cerundolo V. NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J Immunol 2003 Nov 15; 171: 5140-5147. (PMID: 14607913) Download PDF

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2003
Major Discovery
BORTEZOMIB (VELCADE) APPROVED FOR MULTIPLE MYELOMA TREATMENT
Details
November 10, 2003
Major Discovery
BORTEZOMIB (VELCADE) APPROVED FOR MULTIPLE MYELOMA TREATMENT
FDA approves the drug bortezomib (Velcade) for the treatment of multiple myeloma. Bortezomib represents a new class of targeted agents that inhibit proteasomes, structures inside cells that degrade proteins.
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2003
Treatment Approved
TOSITUMOMAB (BEXXAR) APPROVED TO TREAT NON-HODGKIN LYMPHOMA
Details
November 10, 2003
Treatment Approved
TOSITUMOMAB (BEXXAR) APPROVED TO TREAT NON-HODGKIN LYMPHOMA
Tositumomab (Bexxar), a radionuclide-linked mouse anti-human CD19 monoclonal antibody to treat non-Hodgkin lymphoma, is approved by the FDA.
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2003
Major Discovery
DISCOVERIES ON FOXP3
Details
November 10, 2003
Major Discovery
DISCOVERIES ON FOXP3

2003-shimon-sakaguchi.jpgShimon Sakaguchi and colleagues report that the transcription factor Foxp3 is a key regulatory gene for the development of regulatory T cells.[i] Soon after, two papers, by Alexander Rudensky[ii] and by Roli Khattri and Fred Ramsdell,[iii] report in Nature Immunology that Foxp3 is expressed by CD4+CD25+ regulatory T cells and programs their development and function.
 



[i] Hori S, Nomura T, Sakaguchi S.Control of regulatory T cell development by the transcription factor Foxp3. Science 2003 Feb 14; 299: 1057-1061. (PMID: 12522256)

[ii] Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunol 2003 Apr; 4: 330-336. (PMID: 12612578)

[iii] Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nature Immunol 2003 Apr; 4: 330-336. (PMID: 12612581)

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2003
Major Discovery
DISCOVERIES ON IDO BOOST THE EFFICACY OF CANCER VACCINES
Details
November 10, 2003
Major Discovery
DISCOVERIES ON IDO BOOST THE EFFICACY OF CANCER VACCINES

2003-Benoit-Van-den-Eynde.jpgBenoit Van den Eynde shows that tumors frequently express tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) and thereby resist immune rejection. This work opens the way to the search for IDO inhibitors to boost the efficacy of cancer vaccines.



Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 2003 Oct; 9: 1269-1274. (PMID: 14502282)

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2003
Major Discovery
DISCOVERIES ON A CTLA-4-SPECIFIC ANTIBODY
Details
November 10, 2003
Major Discovery
DISCOVERIES ON A CTLA-4-SPECIFIC ANTIBODY

2003-CTLA-4-specific-antibody.jpgA CTLA-4-specific antibody, inhibiting the CTLA-4-mediated immune checkpoint, induces clinical regressions in patients with advanced melanoma (but also causes immune-related toxicity).



Hodi FS, Mihm MC, Soiffer RJ, Haluska FG, Butler M, Seiden MV, Davis T, Henry-Spires R, MacRae S, Willman A, Padera R, Jaklitsch MT, Shankar S, Chen TC, Korman A, Allison JP, Dranoff G. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci U S A 2003 Apr 15; 100: 4712-4717. (PMID: 12682289) Download PDF

 

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2003
Awards & Honors
CRI'S 2003 COLEY AWARD GOES TO DISCOVERIES ON TOLL-LIKE RECEPTORS
Details
November 10, 2003
Awards & Honors
CRI'S 2003 COLEY AWARD GOES TO DISCOVERIES ON TOLL-LIKE RECEPTORS
CRI presents the Coley Award to Jules A. Hoffmann, Bruno Lemaitre, Charles A. Janeway, and Ruslan Medzhitov for their discoveries about Toll-like receptors.
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2003
Major Discovery
DATA FIRST PROVIDED INDICATING THE RELATIONSHIP BETWEEN TUMOR IMMUNITY AND OVARIAN PATIENT OUTCOMES
Details
November 10, 2003
Major Discovery
DATA FIRST PROVIDED INDICATING THE RELATIONSHIP BETWEEN TUMOR IMMUNITY AND OVARIAN PATIENT OUTCOMES

2003-George-Coukos.jpgGeorge Coukos and colleagues provide the first data indicating a relationship between tumor immunity and ovarian patient outcomes, reporting that the presence of tumor-infiltrating lymphocytes in the primary tumor strongly correlated with patient survival.



Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003 Jan 16; 348: 203-213. (PMID: 12529460)

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2003
Awards & Honors
DISCOVERIES ON AN E2A- FACTOR BINDING SEQUENCE CAGGTG
Details
November 10, 2003
Awards & Honors
DISCOVERIES ON AN E2A- FACTOR BINDING SEQUENCE CAGGTG
Nancy Michael, Atsushi Tanaka, Ursula Storb, and colleagues (including 2009-2012 CRI Fellow Prashant Kodgire) show that an E2A- factor binding sequence, CAGGTG, is a strong enhancer of somatic hypermutation of Ig genes, without enhancing transcription, and is sufficient to attract AID.
Michael N, Shen HM, Longerich S, Kim N, Longacre A, Storb U. The E-box motif, CAGGTG, enhances somatic hypermutation without enhancing transcription. Immunity 2003 Aug; 19: 235-242. (PMID: 12932357)

Tanaka A, Shen H, Ratnam S, Kodgire P, Storb U. Targeting of somatic hypermutation through CAGGTG cis-elements. J Exp Med 2010 Feb 15; 207: 405-415. (PMID: 20100870)
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2002
Treatment Approved
THE FIRST RADIONUCLIDE-LINKED MONOCLONAL ANTIBODY APPROVED TO TREAT NON-HODGKIN LYMPHOMA
Details
November 10, 2002
Treatment Approved
THE FIRST RADIONUCLIDE-LINKED MONOCLONAL ANTIBODY APPROVED TO TREAT NON-HODGKIN LYMPHOMA
The first radionuclide-linked monoclonal antibody (ibritumomab tiuxetan, Zevalin) is approved by the FDA (anti-CD20 on B cells) to treat non-Hodgkin lymphoma.
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2002
Field Milestone
THE FIRST CLINICAL TRIALS USING MONOCLONAL ANTIBODIES PUBLISHED
Details
November 10, 2002
Field Milestone
THE FIRST CLINICAL TRIALS USING MONOCLONAL ANTIBODIES PUBLISHED

2002-CTLA-4-blockade.jpgThe first clinical trials using monoclonal antibodies to induce CTLA-4 blockade in patients with malignant melanoma are published.



Fong L, Small EJ. Anti-cytotoxic T-lymphocyte antigen-4 antibody: the first in an emerging class of immunomodulatory antibodies for cancer treatment. J Clin Oncol 2008 Nov 10; 26: 5275-5283. (PMID: 18838703)

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2002
Major Discovery
STUDIES FIRST TO SHOW TUMOR REGRESSIONS CAUSED BY ADOPTIVE T CELL THERAPY
Details
November 10, 2002
Major Discovery
STUDIES FIRST TO SHOW TUMOR REGRESSIONS CAUSED BY ADOPTIVE T CELL THERAPY

Two studies show for the first time that adoptive T cell therapy for patients with advanced melanoma using in vitro-expanded T cells can cause tumor regressions.
 



Yee C, Thompson JA, Byrd D, Riddell SR, Roche P, Celis E, Greenberg PG. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci U S A 2002 Dec 10; 99: 16168-16173. (PMID: 12427970) Download PDF

Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber D, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002 Oct 25; 298: 850-854. (PMID: 12242449) Download PDF

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2002
Major Discovery
RESEARCHERS APPROVED THAT IL-2 IS A POTENT STIMULATOR OF REGULATORY T CELLS
Details
November 10, 2002
Major Discovery
RESEARCHERS APPROVED THAT IL-2 IS A POTENT STIMULATOR OF REGULATORY T CELLS
Researchers demonstrate that IL-2 is a potent stimulator of regulatory T cells (Tregs). IL-2 is a cytokine necessary signal for the development, survival, and expansion of Tregs that downregulate self-reactive lymphocyte responses, thus preventing anemia, enteritis, and other autoimmune sequelae.

Almeida ARM, Legrand N, Papiernik M, Freitas AA. Homeostasis of peripheral CD4+ T cells: IL-2Rα and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers. J Immunol 2002 Nov 1; 169: 4850-4860. (PMID: 12391195) Download PDF
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2002
Major Discovery
DISCOVERY ON SIGNALING MICROCLUSTERS
Details
November 10, 2002
Major Discovery
DISCOVERY ON SIGNALING MICROCLUSTERS

2002-Larry-Samelson.jpgLarry Samelson and colleagues report the description of signaling microclusters containing the TCR with critical signaling enzymes and adapter molecules.



Bunnell SC, Hong DI, Kardon JR, Yamazaki T, McGlade CJ, Barr VA, Samelson LE. T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J Cell Biol 2002 Sep 30; 158: 1263-1275. (PMID: 12356870) Download PDF

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2002
Major Discovery
DISCOVERIES ON LIPID BINDING TO CD1 MOLECULES
Details
November 10, 2002
Major Discovery
DISCOVERIES ON LIPID BINDING TO CD1 MOLECULES

2002-Vincenzo-Cerundolo-1.jpgVincenzo Cerundolo and colleagues report on studies of the structural, kinetic, and functional analysis of lipid binding to CD1 molecules. To gain insights into the structure and function of CD1 molecules, the researchers applied two novel refolding protocols and were able to solve the crystal structure of CD1b molecules with distinct lipid antigens[i] and CD1d molecules loaded with the NKT cell agonist alphaGalactosylCeramide.[ii] These structures clarified for the first time the ligand-binding mechanisms of CD1b via a network of four interlinked hydrophobic channels, which provide a unique adaptable system required to present a broad range of ligands and the ability of CD1d molecules to undergo conformational change.
 



[i] Gadola SD, Zaccai NR, Harlos K, Shepherd D, Castro-Palomino JC, Ritter G, Schmidt RR, Jones EY, Cerundolo V. Structure of human CD1b with bound ligands at 2.3 A, a maze for alkyl chains. Nat Immunol 2002 Aug; 3: 721-726. (PMID: 12118248)

[ii] Koch M, Stronge VS, Shepherd D, Gadola SD, Mathew B, Ritter G, Fersht AR, Besra GS, Schmidt RR, Jones EY, Cerundolo V. The crystal structure of human CD1d with and without alpha-galactosylceramide. Nat Immunol 2005 Aug; 6: 819-826. (PMID: 16007090)

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2002
Major Discovery
DISCOVERY OF IMMUNIZATION AMONG STAGE IV MELANOMA PATIENTS
Details
November 10, 2002
Major Discovery
DISCOVERY OF IMMUNIZATION AMONG STAGE IV MELANOMA PATIENTS

2002-Giorgio-Parmiani.jpgPramod Srivastava, Giorgio Parmiani, and colleagues report that immunization with autologous tumor-derived gp96-peptide complexes elicits tumor regression in stage IV melanoma patients, without any immunization-related adverse events.
 



Belli R, Testori A, Rivoltini L, Maio M, Andreola G, Sertoli MR, Gallino G, Piris A, Cattelan A, Lassari I, Carrabba M, Scita G, Santantonio C, Pilla L, Tragni G, Lombardo C, Arienti F, Marchianò A, Bertolini F, Cova A, Lamaj E, Ascani L, Camerini R, Corsi M, Cascinelli N, Lewis JJ, Srivastava PK, Parmiani G. Vaccination of metastatic melanoma patients with autologous Tumor-derived heat shock protein gp96-peptide complexes. J Clin Oncol 2002 Oct 15 ; 20: 4169-4180. (PMID: 12377960)
 

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2002
Awards & Honors
CRI'S 2002 COLEY AWARD
Details
November 10, 2002
Awards & Honors
CRI'S 2002 COLEY AWARD
CRI presents the Coley Award to Lewis L. Lanier, David H. Raulet, and Mark J. Smyth.
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2002
Major Discovery
DISCOVERIES ON FC RECEPTOR POLYMORPHISMS
Details
November 10, 2002
Major Discovery
DISCOVERIES ON FC RECEPTOR POLYMORPHISMS
Patients with Fc receptor polymorphisms show higher clinical responses to CD20-specific and EGFR-specific monoclonal antibodies, indicating that Fc receptor-mediated immune responses are crucial to their anti-tumor activity.
 

Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P, Colombat P, Watier H. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 2002 Feb 1; 99: 754-758. (PMID: 11806974) Download PDF

Zhang W, Gordon M, Schultheis AM, Yang DY, Nagashima F, Azuma M, Chang HM, Borucka E, Lurje G, Sherrod AE, Iqbal S, Groshen S, Lenz HJ. FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. Zhang W et al. J Clin Oncol 2007 Aug 20; 25: 3712-3718. (PMID: 17704420)
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2001
Field Milestone
REVIVAL OF THE THEORY OF CANCER IMMUNOSURVEILLANCE
Details
November 10, 2001
Field Milestone
REVIVAL OF THE THEORY OF CANCER IMMUNOSURVEILLANCE
The theory of cancer immunosurveillance is revived with the publications by Robert D. Schreiber and Lloyd J. Old (with CRI Fellow Hiroaki Ikeda) and by Mark J. Smyth demonstrating that mice lacking interferon-gamma, IFN-gamma receptor, or IFN-gamma-producing cells types[i] or perforin[ii] have increased susceptibility to B cell lymphomas. These studies help underpin the importance of the immune system in cancer development and revive the theory of “cancer immunosurveillance.”


[i] Shankaran S, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD. IFN-gamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 2001 Apr 26; 410: 1107-1111. (PMID: 11323675)

[ii] Smyth MJ, Thia KY, Street SE, MacGregor D, Godfrey DI, Trapani JA. Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma. J Exp Med 2000 Sep 4; 192: 755-760. (PMID: 10974040) Download PDF

Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, Kawano T, Pelikan SB, Crowe NY, Godfrey DI. Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med 2000 Feb 21; 191: 661-668. (PMID: 10684858) Download PDF
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2001
Major Discovery
THE CRITICAL ROLE OF TRAIL IN IMMUNE SURVEILLANCE OF CANCER DEMONSTRATED
Details
November 10, 2001
Major Discovery
THE CRITICAL ROLE OF TRAIL IN IMMUNE SURVEILLANCE OF CANCER DEMONSTRATED

2001-Mark-J-Smyth.jpgResearchers, including Mark J. Smyth, provide the first demonstration that TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is critical in immune surveillance of cancer.



Takeda K, Hayakawa Y, Smyth MJ, Kayagaki N, Yamaguchi N, Kakuta S, Iwakura Y, Yagita H, Okumura K. Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver NK cells. Nature Medicine 2001 Jan 7; 7: 94-100. (PMID: 11135622)

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2001
Major Discovery
A NEW MECHANISM ESTABLISHED FOR HOW NATURAL KILLER CELLS RECOGNIZE TUMOR CELLS
Details
November 10, 2001
Major Discovery
A NEW MECHANISM ESTABLISHED FOR HOW NATURAL KILLER CELLS RECOGNIZE TUMOR CELLS

2002-Lewis-L-Lanier.jpgDavid Raulet and Lewis Lanier, separately, show that tumor cells expressing ligands for the natural killer cell activating receptor NKG2D are destroyed by natural killer cells in vivo, establishing a new mechanism for how natural killer cells recognize tumor cells.
 



Diefenbach A, Jensen ER, Jamieson AM, Raulet DH. Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature 2001 Sep 13; 413: 165-171. (PMID: 11557981)

Cerwenka A, Baron JL, Lanier LL. Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo. Proc Natl Acad Sci U S A 2001 Sep 25; 98: 11521-11526. (PMID: 11562472) Download PDF

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2001
Major Discovery
A NEW MECHANISM FOR HOW NATURAL KILLER CELLS RECOGNIZE TUMOR CELLS ESTABLISHED
Details
November 10, 2001
Major Discovery
A NEW MECHANISM FOR HOW NATURAL KILLER CELLS RECOGNIZE TUMOR CELLS ESTABLISHED

2001-NKG2D.jpgDavid Raulet and Lewis Lanier, separately, show that tumor cells expressing ligands for the natural killer cell activating receptor NKG2D are destroyed by natural killer cells in vivo, establishing a new mechanism for how natural killer cells recognize tumor cells.
 



Diefenbach A, Jensen ER, Jamieson AM, Raulet DH. Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature 2001 Sep 13; 413: 165-171. (PMID: 11557981)

Cerwenka A, Baron JL, Lanier LL. Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo. Proc Natl Acad Sci U S A 2001 Sep 25; 98: 11521-11526. (PMID: 11562472) Download PDF

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2001
Major Discovery
THE SECOND INDEPENDENT ADJUVANT INTERFERON TRIAL REPORTED
Details
November 10, 2001
Major Discovery
THE SECOND INDEPENDENT ADJUVANT INTERFERON TRIAL REPORTED

2001-John-M-Kirkwood-1.jpgJohn M. Kirkwood and ECOG report the second independent adjuvant interferon trial to improve both relapse-free and overall survival compared to a vaccine control. (E1694)

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2001
Major Discovery
DISCOVERIES ON BCG REFRACTORY BLADDER CANCER
Details
November 10, 2001
Major Discovery
DISCOVERIES ON BCG REFRACTORY BLADDER CANCER

2001-Michael-A-O-Donnell_1.jpgMichael O’Donell reports on the efficacy of the combination of interferon-alpha 2b plus low dose BCG in patients with BCG refractory bladder cancer.



O’Donell MA, Krohn J, DeWolf WC. Salvage intravesical therapy with interferon-alpha 2b plus low dose bacillus Calmette-Guerin is effective in patients with superficial bladder cancer in whom bacillus Calmette-Guerin alone previously failed. J Urol 2001 Oct; 166: 1300-1305. (PMID: 11547062)

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2001
Major Discovery
3D STRUCTURE OF THE CTLA-4 IN COMPLEX WITH ITS LIGAND B SOLVED
Details
November 10, 2001
Major Discovery
3D STRUCTURE OF THE CTLA-4 IN COMPLEX WITH ITS LIGAND B SOLVED

2001-CTLA-4-in-complex-with-its-ligand-B-7.jpgReporting in the journal Nature, Stanley G. Nathenson and his colleague Steven C. Almo, at Albert Einstein College of Medicine,[i] and William S. Somers and colleagues at Wyeth Research in Cambridge, MA,[ii] crystallize and solve the 3D structure of the powerful negative T cell regulatory molecule CTLA-4 in complex with its ligand B-7. This revealing structure demonstrates that CTLA-4 occurrs as a dimer with bivalent properties allowing it to bind 2 B-7 dimers and form an alternating array likely important for its negative signaling capabilities. CTLA-4 has since been shown to have important therapeutic uses. Dr. Nathenson and colleagues also solved the 3D structure of the critical T cell molecules PD-1/PD-L1. Strategies to manipulate the PD-1 pathway are currently being tested in clinical trials for cancer and HIV/AIDS.
 



[i] Schwartz J-C D, Zhang X, Fedorov AA, Nathenson SG, Almo SC. Structural basis for co-stimulation by the human CTLA-4/B7-2 complex. Nature 2001 Mar 29; 410: 604-608. (PMID: 11279501)

[ii] Stamper CC, Zhang Y, Tobin JF, Erbe DV, Ikemizu S, Davis SJ, Stahl ML, Seehra J, Somers WS, Mosyak L. Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses. Nature 2001 Mar 29; 410: 608-611. (PMID: 11279502)

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2001
Treatment Approved
CRI PROVIDES A PILOT GRANT FOR PRECLINICAL STUDIES
Details
November 10, 2001
Treatment Approved
CRI PROVIDES A PILOT GRANT FOR PRECLINICAL STUDIES

2001-Jean-Pierre-Mach.jpgCRI provides a pilot grant to Jean-Pierre Mach for preclinical studies to test a new cancer immunotherapy strategy using anti-tumor antibody fragments conjugated to antigenic MHC/peptide complexes.

“The Cancer Research Institute plays a very important role to support the work of scientists who have original ideas of cancer immunotherapy, which are promising, but not yet proven enough for obtaining financial support from commercial groups. In our laboratory we had the idea of localizing on tumor cells, with specific monoclonal antibodies, molecules, such as Major Histocompatibility Complexe (MHC), loaded with viral peptides, which can activate the T lymphocytes to attack the target tumor cells. Thank to a 3 years support provided by CRI, we were able to make the first demonstration of this therapeutic strategy in experimental animals.[i] Furthermore, [we] demonstrated that an MHC like molecule, called CD1d, loaded with a glycolipid ligand, called alphaGalCer, also targeted to the tumor cells by monoclonal antibodies, was capable to specifically inhibit tumor growth in vivo and to give a sustained activation of the Natural Killer Cells known to be important in the innate immunity.[ii] Later this project was sponsored by industry, and may become a clinically useful form of cancer therapy; but the role of CRI in the initiation of this project was essential.” – Jean-Pierre Mach



[i] Donda A, Cesson V, Mach JP, Corradin G, Primus FJ, Robert B. In vivo targeting of an anti-tumor antibody coupled to antigenic MHC class I complexes induces specific growth inhibition and regression of established syngeneic tumor grafts. Cancer Immun 2003 Aug 14; 3: 11. (PMID: 12916958) Download PDF

[ii] Stirnemann K, Romero JF, Baldi L, Robert B, Cesson V, Besra GS, Zauderer M, Wurm F, Corradin G, Mach JP, Macdonald HR, Donda A. Sustained activation and tumor targeting of NKT cells using a CD1d-anti-HER2-scFv fusion protein induce antitumor effects in mice. J Clin Invest 2008 Mar 11; 118: 994-1005. (PMID: 18259610) Download PDF

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2001
Treatment Approved
ALEMTUZUMAB (CAMPATH 1H) APPROVED BY THE FDA TO TREAT CHRONIC LYMPHOCYTIC LEUKEMIA
Details
November 10, 2001
Treatment Approved
ALEMTUZUMAB (CAMPATH 1H) APPROVED BY THE FDA TO TREAT CHRONIC LYMPHOCYTIC LEUKEMIA
Alemtuzumab (Campath 1H), a humanized monoclonal antibody directed against CD52 on B, T, and NK cells and monocytes, is approved by the FDA for the treatment of chronic lymphocytic leukemia.
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2001
Field Milestone
IMATINIB MESYLATE PROVED TO BE EFFECTIVE AGAINST CHRONIC MYELOGENOUS LEUKEMIA
Details
November 10, 2001
Field Milestone
IMATINIB MESYLATE PROVED TO BE EFFECTIVE AGAINST CHRONIC MYELOGENOUS LEUKEMIA
The drug imatinib mesylate (Gleevec) is shown to be effective against chronic myelogenous leukemia (CML). Imatinib mesylate is the first anti-cancer drug developed specifically to target the molecular defect that causes a particular type of cancer.
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2001
Major Discovery
IDENTIFICATION OF TWO LIGANDS FOR PD-1
Details
November 10, 2001
Major Discovery
IDENTIFICATION OF TWO LIGANDS FOR PD-1

2001-Lieping-Chen.jpgTwo ligands for PD-1 are identified: B7-H1 (also known as PD-L1), by Lieping Chen and Tasuko Honjo, and B7-DC (also known as PD-L2), by Drew Pardoll and Tasuko Honjo.



Tseng S-Y, Otsuji M, Gorski K, Huang X, Slansky JE, Pai SI, Shalabi A, Shin T, Pardoll DM, Tsuchiya H. B7-Dc, a new dendritic cell molecule with potent costimulatory properties for T cells. J Exp Med 2001 Apr 2; 193: 839-846. (PMID: 11283156)
 

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2001
CRI Milestone
CANCER VACCINE COLLABORATIVE (CVC) ESTABLISHED
Details
November 10, 2001
CRI Milestone
CANCER VACCINE COLLABORATIVE (CVC) ESTABLISHED

2001-Cancer-Vaccine-Collaborative-(CVC).jpgThe Cancer Research Institute and the Ludwig Institute for Cancer Research establish the Cancer Vaccine Collaborative (CVC) with cancer vaccine programs in non-small cell lung cancer at Weill Medical College of Cornell University, in melanoma at Columbia Presbyterian Medical Center, and in prostate cancer at Mount Sinai Medical Center.

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2001
Awards & Honors
CRI'S 2001 COLEY AWARD
Details
November 10, 2001
Awards & Honors
CRI'S 2001 COLEY AWARD

2001-Robert-D-Schreiber.jpgCRI presents the Coley Award to Robert D. Schreiber.

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1990s
1999
Major Discovery
EVIDENCE INDICATES THAT RECEPTOR PD-1 IS AN IMMUNE CHECKPOINT
Details
November 10, 1999
Major Discovery
EVIDENCE INDICATES THAT RECEPTOR PD-1 IS AN IMMUNE CHECKPOINT
Tasuku Honjo and colleagues demonstrate that PD-1 knockout mice develop autoimmune syndromes, suggesting that the receptor PD-1 is an immune checkpoint.
 

Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999 Aug 11; 11: 141-151. (PMID: 10485649)

Nishimura H, Okazaki T, Tanaka Y, Nakatini K, Hara M, Matsumori A, Sasayama S, Mizoguchi A, Hiai H, Minato N, Honjo T. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 2001 Jan 12; 291: 319-322. (PMID: 11209085)
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1999
Major Discovery
DISCOVERIES ON THE GENE TH-POK
Details
November 10, 1999
Major Discovery
DISCOVERIES ON THE GENE TH-POK

1999-Dietmar-J-Kappes.jpgDietmar J. Kappes discovers a mouse with a mutation in a master regulator gene controlling T cell fate. Six years later, he identifies the gene as Th-POK, and later shows that its disregulation causes lymphoid transformation. This finding is significant in linking how cells develop with how cancers develop.
 



Keefe R, Dave V, Allman D, Wiest D, Kappes DJ. Regulation of lineage commitment distinct from positive selection. Science 1999 Nov 5; 286: 1149-1193. (PMID: 10550051)

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1999
Major Discovery
NEW DISCOVERY OF REGULATORY T CELLS
Details
November 10, 1999
Major Discovery
NEW DISCOVERY OF REGULATORY T CELLS

eiichi-nakayama-2016-206x236.jpgEiichi Nakayama and colleagues first report involvement of regulatory T cells (Tregs) in the human tumor immune response.



Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res 1999 Jul 1; 59: 3128-3133. (PMID: 10397255) Download PDF

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1999
Major Discovery
DISCOVERY ON NY-ESO-1-SPECIFIC ANTIBODY
Details
November 10, 1999
Major Discovery
DISCOVERY ON NY-ESO-1-SPECIFIC ANTIBODY

1999-Elke-Jaege.jpgElke Jaeger, Elizabeth Stockert, Yao-Tseng Chen, Julia Karbach, Dirk Jaeger, Gerd Ritter, Lloyd J. Old, and Alex Knuth show that NY-ESO-1-specific antibody responses depend on the presence of NY-ESO-1-positive tumor cells.



Jäger E, Stockert E, Zidianakis Z, Chen YT, Karbach J, Jäger D, Arand M, Ritter G, Old LJ, Knuth A. Humoral immune responses of cancer patients against “Cancer-Testis” antigen NY-ESO-1: correlation with clinical events. Int J Cancer 1999 Oct 22; 84: 506-510. (PMID: 10502728)

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1999
Major Discovery
STAT5 PROTEINS PROVED TO BE ESSENTIAL MEDIATORS OF IL-2 SIGNALING IN T CELLS
Details
November 10, 1999
Major Discovery
STAT5 PROTEINS PROVED TO BE ESSENTIAL MEDIATORS OF IL-2 SIGNALING IN T CELLS

1999-James-N-Ihle.jpgJames N. Ihle and colleagues demonstrate that the Stat5 proteins, redundantly, are essential mediators of IL-2 signaling in T cells.



Moriggl R, Topham DJ, Teglund S, Sexl V, McKay C, Wang D, Hoffmeyer A, van Deursen J, Sangster MY, Bunting KD, Grosveld GC, Ihle JN. 1999. Stat5 Is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity 10: 249-59

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1999
Major Discovery
CRYSTAL STRUCTURE OF A T CELL RECEPTOR DETERMINED
Details
November 10, 1999
Major Discovery
CRYSTAL STRUCTURE OF A T CELL RECEPTOR DETERMINED
Ellis L. Reinherz and colleauges determine the crystal structure of a T cell receptor in complex with peptide and MHC class II.

Reinherz EL, Tan K, Tang L, Kern P, Liu J-h, Xiong Y, Hussey RE, Smolyar A, Hare B, Zhang R, Joachimiak A, Chang H-C, Wagner G, Wang J-h. 1999. The crystal structure of a T cell receptor in complex with peptide and MHC class II. Science 286: 1913-21
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1999
Major Discovery
FIRST EVIDENCE PROVIDED ON GENE-EXPRESSION PROFILING
Details
November 10, 1999
Major Discovery
FIRST EVIDENCE PROVIDED ON GENE-EXPRESSION PROFILING

1999-Eric-S-Lander.jpgEric S. Lander and colleagues provide the first evidence that gene-expression profiling can distinguish between cancer types. In addition to distinguishing between two types of leukaemia on the basis of expression profile differences, the method could also predict their responsiveness to chemotherapy.
 



Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeck M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES. 1999. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286: 531-7

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1999
Awards & Honors
CRI ANNOUNCED ITS 1999 COLEY AWARD
Details
November 10, 1999
Awards & Honors
CRI ANNOUNCED ITS 1999 COLEY AWARD
CRI presents the 1999 Coley Award to James E. Darnell Jr., Ian M. Kerr, Richard A. Lerner, George R. Stark, and Greg Winter.
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1999
CRI Milestone
CRI'S CANCER ANTIGEN DISCOVERY COLLABORATIVE ESTABLISHED
Details
November 10, 1999
CRI Milestone
CRI'S CANCER ANTIGEN DISCOVERY COLLABORATIVE ESTABLISHED
CRI establishes the Cancer Antigen Discovery Collaborative (CADC).
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1998
Field Milestone
THE ACADEMY OF CANCER IMMUNOLOGY ESTABLISHED
Details
November 10, 1998
Field Milestone
THE ACADEMY OF CANCER IMMUNOLOGY ESTABLISHED

1998-The-Academy-of-Cancer-Immunology-established.jpgThe Academy of Cancer Immunology is established with 20 founding members, including James P. Allison, Thierry Boon, Jean-Charles Cerottini, Philip D. Greenberg, Alan N. Houghton, Georg Klein, Alexander Knuth, Carl F. Nathan, Herbert F. Oettgen, Lloyd J. Old, Drew M. Pardoll, Michael Pfreundschuh, Steven A. Rosenberg, Stuart F. Schlossman, Hans Schreiber, Robert D. Schreiber, Hiroshi Shiku, Pramod K. Srivastava, Toshitada Takahashi, Giorgio Trinchieri, and Rolf Zinkernagel.

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1998
Major Discovery
NEW FINDINGS ON CD4+CD25+ T CELLS
Details
November 10, 1998
Major Discovery
NEW FINDINGS ON CD4+CD25+ T CELLS
Angela M. Thornton and Ethan M. Shevach present data to support the concept that CD4+CD25+ T cells in normal mice may represent a distinct lineage of “professional” suppressor cells.
 

Thornton AM, Shevach EM. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 1998 Jul 20; 188: 287-296. (PMID: 9670041) Download PDF
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1998
Major Discovery
A LANDMARK STUDY PUBLISHED ON CD8+ TILS
Details
November 10, 1998
Major Discovery
A LANDMARK STUDY PUBLISHED ON CD8+ TILS

1998-Haruo-Ohtani.jpgHaruo Ohtani and colleagues at the Kitasato University School of Medicine in Japan publish a landmark study showing that the presence and location of CD8+ tumor-infiltrating lymphocytes (TILs) correlates with prognosis in colon cancers, specifically that the accumulation of CD8+ T cells within the tumor predicted improved patient survival, whereas accumulation of the same cells in the tumor periphery did not correlate with survival.


Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ontani H. CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 1998 Aug 15; 58: 3491-3494. (PMID: 9721846) Download PDF

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1998
Major Discovery
FIRST EVIDENCE OF STRONG INTEGRATED IMMUNE RESPONSES AGAINST NY-ESO-1 PROVIDED
Details
November 10, 1998
Major Discovery
FIRST EVIDENCE OF STRONG INTEGRATED IMMUNE RESPONSES AGAINST NY-ESO-1 PROVIDED
Elke Jaeger, Yao-Tseng Chen, Julia Karbach, Dirk Jaeger, Hisashi Wada, Yuji Noguchi, Elizabeth Stockert, Lloyd J. Old, and Alex Knuth provide the first evidence of strong integrated immune responses against NY-ESO-1 in patients and the identification of the first HLA-A2-binding epitope.
 

Jäger E, Chen YT, Drijfhout JW, Karbach J, Ringhoffer M, Jäger D, Arand M, Wada H, Noguchi Y, Stockert E, Old LJ, Knuth A. Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes. J Exp Med 1998 Jan 19; 187: 265-270. (PMID: 9432985) Download PDF
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1998
Major Discovery
IDENTIFICATION OF THE CRITICAL T CELL SUBSTRATE LAT
Details
November 10, 1998
Major Discovery
IDENTIFICATION OF THE CRITICAL T CELL SUBSTRATE LAT
Larry Samelson and colleagues report the identification of the critical T cell substrate LAT.
 

Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE. LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell 1998 Jan 9; 92: 83-92. (PMID: 9489702)
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1998
Major Discovery
GENETIC BASIS LINKING TLR4 ESTABLISHED TO IDENTIFY MICROBES
Details
November 10, 1998
Major Discovery
GENETIC BASIS LINKING TLR4 ESTABLISHED TO IDENTIFY MICROBES

1998-Bruce-A-Beutler.jpgBruce A. Beutler establishes the genetic basis linking toll-like receptor 4 (TLR4) to the identification of microbes.



Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998 Dec 11; 282: 2085-2088. (PMID: 9851930)

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1998
Major Discovery
PROTO-ONCOGENE BCL6 FIRST SHOWED AS A TARGET FOR SOMATIC HYPERMUTATION
Details
November 10, 1998
Major Discovery
PROTO-ONCOGENE BCL6 FIRST SHOWED AS A TARGET FOR SOMATIC HYPERMUTATION

Hong Ming Shen, Beverly Baron, and Ursula Storb show for the first time that a non-Ig gene, the proto-oncogene BCL6, is a target for somatic hypermutation, thus implying SHM as an inducer of certain B cell leukemias.



Shen H, Peters A, Baron B, Zhu X, Storb U. Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes. Science 1998 Jun 12; 280: 1750-1752. (PMID: 9624052)

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1998
Major Discovery
NEW FINDINGS ON THE USE OF TETRAMERIC SOLUBLE CLASS I/PEPTIDE COMPLEXES
Details
November 10, 1998
Major Discovery
NEW FINDINGS ON THE USE OF TETRAMERIC SOLUBLE CLASS I/PEPTIDE COMPLEXES

2002-Vincenzo-Cerundolo.jpgThe laboratory of Vincenzo Cerundolo is the first group to report the use of tetrameric soluble class I/peptide complexes (tetramers) for the identification of tumor-specific cytotoxic T lymphocytes (CTLs), and subsequently shows that these novel reagents allow rapid and accurate analysis of human CTL responses.
 



Dunbar PR, Ogg GS, Chen J, Rust N, van der Bruggen P, Cerundolo V. Direct isolation, phenotyping and cloning of low-frequency antigen-specific cytotoxic T lymphocytes from peripheral blood. Curr Biol 1998 Mar 26; 8: 413-416. (PMID: 9545200)

Dunbar PR, Chen JL, Chao D, Rust N, Teisserenc H, Ogg GS, Romero P, Weynants P, Cerundolo V. Cutting edge: rapid cloning of tumor-specific CTL suitable for adoptive immunotherapy of melanoma. J Immunol 1999 Jun 15; 162: 6959-6962. (PMID: 10358133) Download PDF

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1998
Major Discovery
NEW DISCOVERIES ON TUMOR-SPECIFIC CTLS
Details
November 10, 1998
Major Discovery
NEW DISCOVERIES ON TUMOR-SPECIFIC CTLS

In collaboration with Pedro Romero, Vincenzo Cerundolo and colleagues demonstrate that, unlike virus-specific CTLs, the highest frequency of tumor-specific CTLs can be found in tumor-infiltrated lymph nodes.[i] Extending these studies to vitiligo patients, they then demonstrate using MHC class I tetramers that vitiligo patients’ PBL (peripheral blood lymphocytes) have a high frequency of skin-homing melanocyte-specific CTLs.[ii] Importantly, these results illustrate the interphase between tumor immunity and autoimmunity, since several tumor antigenic proteins are co-expressed by normal and tumor cells.
 



[i] Romero P, Dunbar PR, Valmori D, Pittet M, Ogg GS, Rimoldi D, Chen JL, Lienard D, Cerottini JC, Cerundolo V. Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-specific cytolytic T lymphocytes. J Exp Med 1998 Nov 2; 188: 1641-1650. (PMID: 9802976) Download PDF

[ii] Ogg GS, Rod Dunbar P, Romero P, Chen JL, Cerundolo V. High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo. J Exp Med 1998 Sep 21; 188: 1203-1208. (PMID: 9743539) Download PDF

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1998
Major Discovery
IMMUNOLOGICAL SYNAPSE CREATED
Details
November 10, 1998
Major Discovery
IMMUNOLOGICAL SYNAPSE CREATED

1998-Abraham-Kupfer.jpgAbraham Kupfer describes the three-dimensional structure of supramolecular activation clusters (SMACs), the interface between an antigen presenting cell and a lymphocyte (including key molecules the T cell receptor and the major histocompatibility complex), [i] later coined the immunological synapse and further elucidated by Arash Grakoui, Michael Dustin, Paul Allen, and Andrey Shaw.[ii]
 



[i] Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 1998 Sep 3; 395: 82-86. (PMID: 9738502)

Dustin ML, Olszowy MW, Holdorf AD, Li J, Bromley S, Desai N, Widder P, Rosenberger F, van der Merwe PA, Allen PM, Shaw AS. A novel adapter protein orchestrates receptor patterning and cytoskeletal polarity in T cell contacts. Cell 1998 Sep 4; 94: 667-677. (PMID: 9741631)

[ii] Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML. 1999. The immunological synapse: A molecular machine controlling T cell activation. Science 285: 221-2

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1998
Major Discovery
DISCOVERIES OF C-REL
Details
November 10, 1998
Major Discovery
DISCOVERIES OF C-REL

1998-Hsiou-Chi-Liou.jpgHsiou-Chi Liou and colleagues find that c-Rel, a lymphoid-specific member of the NF-kappaB/Rel family of transcriptional factors, is essential for B lymphocyte survival and cell cycle progression,[i] and that it is important for inducible cytokine and cytokine receptor expression and a key regulator of early activation and proliferation in T cells.[ii]
 



[i] Tumang JR, Owyang A, Andjelic S, Jin Z, Hardy RR, Liou M-L, Liou H-C. 1998. c-Rel is essential for B lymphocyte survival and cell cycle progression. European Journal of Immunology 28: 4299-312

[ii] Liou H-C, Jin Z, Tumang JR, Andjelic S, Smith KA, Liou M-L. 1999. c-Rel is crucial for lymphocyte proliferation but dispensable for T cell effector function. International Immunology 11: 361-71 Download PDF

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1998
Treatment Approved
TRASTUZUMAB (HERCEPTIN) APPROVED TO TREAT METASTATIC BREAST CANCER
Details
November 10, 1998
Treatment Approved
TRASTUZUMAB (HERCEPTIN) APPROVED TO TREAT METASTATIC BREAST CANCER

1998-Trastuzumab-(Herceptin).jpgTrastuzumab (Herceptin), a monoclonal antibody that targets cancer cells that overproduce the HER2/neu oncoprotein, is approved by the FDA for the treatment of metastatic breast cancer.

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1998
CRI Milestone
CRI'S PREDOCTORAL PROGRAM IN TUMOR IMMUNOLOGY ESTABLISHED
Details
November 10, 1998
CRI Milestone
CRI'S PREDOCTORAL PROGRAM IN TUMOR IMMUNOLOGY ESTABLISHED

CRI establishes the Predoctoral Emphasis Pathways in Tumor Immunology program.

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1998
Awards & Honors
CRI ANNOUNCED ITS 1998 COLEY AWARD
Details
November 10, 1998
Awards & Honors
CRI ANNOUNCED ITS 1998 COLEY AWARD

CRI presents the 1998 Coley Award to Klas Kärre, Lorenzo Moretta, and Ralph M. Steinman.

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1997
Major Discovery
THE ROLE OF HUMAN TLR4 IN IMMUNE RESPONSE DISCOVERED
Details
November 10, 1997
Major Discovery
THE ROLE OF HUMAN TLR4 IN IMMUNE RESPONSE DISCOVERED

1989-Charles-Janeway.jpgCharles A. Janeway and Ruslan Medzhitov demonstrate that human TLR4 can mediate the immune response.



Medzhitov R, Preston-Hurlburt P, Janeway CA. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997 Jul 24; 388: 394-397. (PMID: 9237759)

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1997
Major Discovery
NY-ESO-1 DISCOVERED
Details
November 10, 1997
Major Discovery
NY-ESO-1 DISCOVERED

1997-Yao-Tseng-Chen.jpgYao-Tseng Chen, collaborating with researchers in the laboratory of Lloyd J. Old, discovers the antigen New York-ESO-1, or NY-ESO-1. The immunogenicity of NY-ESO-1 is verified by Alex Knuth and Elke Jaeger in Frankfurt.

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1997
Major Discovery
THE ROLE OF THE TRANSCRIPTION FACTOR GATA3/STAT6 DISCOVERED
Details
November 10, 1997
Major Discovery
THE ROLE OF THE TRANSCRIPTION FACTOR GATA3/STAT6 DISCOVERED

1997-Richard-Flavell.jpgRichard Flavell demonstrates the role of the transcription factor GATA3/STAT6 in driving the generation of Th2 type CD4+ T cells.



Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 1997 May 16; 89: 587-596. (PMID: 9160750)

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1997
Major Discovery
A NEW TUMOR NECROSIS FACTOR FAMILY MEMBER TRANCE DISCOVERED
Details
November 10, 1997
Major Discovery
A NEW TUMOR NECROSIS FACTOR FAMILY MEMBER TRANCE DISCOVERED

1997-Yongwon-Choi.jpgYongwon Choi, with Ralph Steinman and others, identifies a new tumor necrosis factor family member TRANCE (later called RANKL),[i] and subsequently demonstrates its role in the immune and bone system, and also in bone-residing cancers such as multiple myelomas.[ii]
 



[i] Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett III FS, Frankel WN, Lee SY, Choi Y. TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinases in T cells. J Biol Chem 1997 Oct 3; 272: 25910-25914. (PMID: 9312132) Download PDF

[ii] Wong BR, Josien R, Lee SY, Sauter B, Li H-L, Steinman RM, Choi Y. TRANCE, a new TNF family member predominantly expressed in T cells, is a dendritic cell specific survival factor. J Exp Med 1997 Dec 15; 186: 2075-2080. (PMID: 9396779) Download PDF

Fuller K, Wong B, Fox S, Choi Y, Chambers TJ. TRANCE is necessary and sufficient for osteoblast-mediated activation of bone resorption in osteoclasts. J Exp Med 1998 Sep 7; 188: 997-1001. (PMID: 9730902) Download PDF

Pearse RN, Sordillo EM, Yaccoby S, Wong BR, Liau DF, Colman N, Michaeli J, Epstein J, Choi Y. Multiple myeloma disrupts the TRANCE/ osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci U S A 2001 Sep 25; 98: 11581-11586. (PMID: 11562486) Download PDF

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1997
Major Discovery
FIRST DEMONSTRATION OF IMMUNOSELECTION IN THE PRESENCE OF ANTIGEN-SPECIFIC CTLS
Details
November 10, 1997
Major Discovery
FIRST DEMONSTRATION OF IMMUNOSELECTION IN THE PRESENCE OF ANTIGEN-SPECIFIC CTLS

Researchers in Frankfurt, including Elke Jaeger, Dirk Jaeger, Julia Karbach, and Alex Knuth provide the first demonstration of immunoselection in vivo in the presence of antigen-specific CTLs.



Jäger E, Ringhoffer M, Altmannsberger M, Arand M, Karbach J, Jäger D, Oesch F, Knuth A. Immunoselection in vivo: independent loss of MHC class I and melanocyte differentiation antigen expression in metastatic melanoma. Int J Cancer 1997 Apr 10; 71: 142-147. (PMID: 9139833)

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1997
Treatment Approved
THE FIRST HUMANIZED MONOCLONAL ANTIBODY APPROVED
Details
November 10, 1997
Treatment Approved
THE FIRST HUMANIZED MONOCLONAL ANTIBODY APPROVED

The first humanized monoclonal antibody (daclizumab, Zenapax) is approved by the FDA.

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1997
Treatment Approved
FIRST MONOCLONAL ANTIBODY FOR CANCER APPROVED
Details
November 10, 1997
Treatment Approved
FIRST MONOCLONAL ANTIBODY FOR CANCER APPROVED

1997-rituxan.jpgThe first monoclonal antibody for cancer (rituximab, Rituxan, directed to CD20 on B lymphocytes) is approved for the treatment of non-Hodgkin lymphoma by the FDA.

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1997
Major Discovery
FIRST CONCLUSIVE EVIDENCE FOR CANCER STEM CELLS REPORTED
Details
November 10, 1997
Major Discovery
FIRST CONCLUSIVE EVIDENCE FOR CANCER STEM CELLS REPORTED

1997-Dominique-Bonnet.jpgDominique Bonnet and John E. Dick report the first conclusive evidence for cancer stem cells, identified in acute myelogenous leukemia (AML).



Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Medicine 1997 Jul; 3: 730-737. (PMID: 9212098)

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1997
Major Discovery
DISCOVERY ON TUMOR-DERIVED HEAT SHOCK PROTEIN-PEPTIDE VACCINES
Details
November 10, 1997
Major Discovery
DISCOVERY ON TUMOR-DERIVED HEAT SHOCK PROTEIN-PEPTIDE VACCINES

1997-Yasuaki-Tamura.jpgYasuaki Tamura, working with colleagues in the laboratory of Pramod Srivastava, demonstrates that tumor-derived heat shock protein-peptide vaccines can be used to treat a wide array of pre-existing tumors in mice.



Tamura Y, Peng P, Liu K, Daou M, Srivastava PK. Immunotherapy of metastatic lung cancer by heat shock protein preparations. Science 1997 Oct 3; 278: 117-120. (PMID: 9311915)

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1997
Major Discovery
CLONING OF THE IΚB KINASES IKK-1 AND IKK-2 REPORTED
Details
November 10, 1997
Major Discovery
CLONING OF THE IΚB KINASES IKK-1 AND IKK-2 REPORTED

Frank Mercurio and Anjana Rao report the cloning of the IκB kinases IKK-1 and IKK-2, the essential upstream regulators of the transcription factor NFκB.



Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, Young D, Barbosa M, Mann M, Manning A, Rao A. IKK-1 and IKK-2, Cytokine-activated IκB kinases essential for NF-κB activation. Science 1997 Oct 31; 278: 860-865. (PMID: 9346484)

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1997
Major Discovery
THE KEY MISSING LINK BETWEEN THE INNATE AND ADAPTIVE IMMUNE RESPONSES PROVIDED
Details
November 10, 1997
Major Discovery
THE KEY MISSING LINK BETWEEN THE INNATE AND ADAPTIVE IMMUNE RESPONSES PROVIDED

Ira Mellman, with Ralph Steinman and others, including Shannon Turley, and Antonio Lanzavecchia provide the first clear demonstration that dendritic cells “mature” in response to microbial products or pro-inflammatory mediators, activating their antigen processing and presentation capacities. By showing that ligands associated with innate immunity enable dendritic cells to initiate T cell responses, this work provided the key missing link between the innate and adaptive immune responses.



Pierre P, Turley SJ, Gatti E, Hull M, Meltzer J, Mirza A, Inaba K, Steinman RM, Mellman I. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature 1997 Aug 21; 388: 787-792. (PMID: 9285592)

Cella M, Engering A, Pinet V, Pieters J, Lanzavecchia A. Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells.Nature 1997 Aug 1; 388: 782-787. (PMID: 9285591)

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1997
Major Discovery
THE KEY MISSING LINK BETWEEN THE INNATE AND ADAPTIVE IMMUNE RESPONSES PROVIDED
Details
November 10, 1997
Major Discovery
THE KEY MISSING LINK BETWEEN THE INNATE AND ADAPTIVE IMMUNE RESPONSES PROVIDED

Ira Mellman, with Ralph Steinman and others, including Shannon Turley, and Antonio Lanzavecchia provide the first clear demonstration that dendritic cells “mature” in response to microbial products or pro-inflammatory mediators, activating their antigen processing and presentation capacities. By showing that ligands associated with innate immunity enable dendritic cells to initiate T cell responses, this work provided the key missing link between the innate and adaptive immune responses.



Pierre P, Turley SJ, Gatti E, Hull M, Meltzer J, Mirza A, Inaba K, Steinman RM, Mellman I. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature 1997 Aug 21; 388: 787-792. (PMID: 9285592)

Cella M, Engering A, Pinet V, Pieters J, Lanzavecchia A. Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells.Nature 1997 Aug 1; 388: 782-787. (PMID: 9285591)

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1997
Awards & Honors
CRI ANNOUNCED ITS 1997 COLEY AWARD
Details
November 10, 1997
Awards & Honors
CRI ANNOUNCED ITS 1997 COLEY AWARD

CRI presents the 1997 Coley Award to Robert L. Coffman, Tim R. Mosmann, and Stuart F. Schlossman.

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1997
Major Discovery
NEW DISCOVERY ON THE HIERARCHICAL ORGANIZATION OF TCR
Details
November 10, 1997
Major Discovery
NEW DISCOVERY ON THE HIERARCHICAL ORGANIZATION OF TCR

1997-Ronald-N-Germain.jpgYasushi Itoh and Ronald N. Germain report studies emphasizing the hierarchical organization of T cell receptor (TCR) signaling thresholds for induction of distinct cytokine responses, and demonstrate that this threshold phenomenon applies to individual cells. The existence of such thresholds suggests that antigen dose may dictate not only the extent, but also the quality of an immune response, by altering the ratios of the cytokines produced by activated T cells.
 



Itoh Y, Germain RN. Single cell analysis reveals regulated hierarchical T cell antigen receptor signaling thresholds and intraclonal heterogeneity for individual cytokine responses of CD4+ T cells. J Exp Med 1997 Aug 29; 186: 757-676. (PMID: 9271591) Download PDF

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1997
Field Milestone
COMPLETE VERSION OF DR. WILLIAM B. COLEY'S PAPERS ARCHIVED
Details
November 10, 1997
Field Milestone
COMPLETE VERSION OF DR. WILLIAM B. COLEY'S PAPERS ARCHIVED

William-Coley_206x236.jpgThe complete papers of Dr. William B. Coley are archived at Yale University.

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1996
Awards & Honors
CRI COLEY AWARD GOES TO THE DISCOVERY OF IL-12
Details
November 10, 1996
Awards & Honors
CRI COLEY AWARD GOES TO THE DISCOVERY OF IL-12

Giorgio-Trinchieri.jpgCRI presents the 1996 Coley Award to Giorgio Trinchieri for the discovery of interleukin-12.

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1996
Treatment Approved
TOPOTECAN APPROVED FOR OVARIAN CANCER TREATMENT
Details
November 10, 1996
Treatment Approved
TOPOTECAN APPROVED FOR OVARIAN CANCER TREATMENT

1996-Topotecan_1.jpgTopotecan is approved by the FDA for the treatment of metastatic ovarian cancer.

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1996
Treatment Approved
IRINOTECAN APPROVED FOR METASTATIC COLORECTAL CANCER
Details
November 10, 1996
Treatment Approved
IRINOTECAN APPROVED FOR METASTATIC COLORECTAL CANCER

1996-irinotecan.jpgThe FDA approves another topoisomerase I inhibitor—irinotecan—for the treatment of metastatic colorectal cancer. (NCI)

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1996
Tools & Technologies
TETRAMER TECHNOLOGY DEFINED
Details
November 10, 1996
Tools & Technologies
TETRAMER TECHNOLOGY DEFINED

1996-Mark-M-Davis.jpgMark M. Davis, at Stanford University Cancer Center, defines tetramer technology, permitting clinicians to monitor patients’ immune responses to cancer vaccines, as well as to study endogenous T cell responses to cancer.

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1996
Major Discovery
DISCOVERY ON REL IN MICE
Details
November 10, 1996
Major Discovery
DISCOVERY ON REL IN MICE

Steve Gerondakis and colleagues establish that Rel (from the c-rel gene) in mice is a positive or negative regulator of transcription in macrophages and that Rel has distinct roles in different macrophage populations.



Grigoriadis G, Zhan Y, Grumont RJ, Metcalf D, Handman E, Cheers C, Gerondakis S. The Rel subunit of NF-kappaB-like transcription factors is a positive and negative regulator of macrophage gene expression: distinct roles for Rel in different macrophage populations. EMBO J 1996 Dec 16; 15: 7099-7107. (PMID: 9003785) Download PDF

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1996
Major Discovery
NEW FINDINGS ON TCR
Details
November 10, 1996
Major Discovery
NEW FINDINGS ON TCR

1996-Leslie-J-Berg.pngLeslie J. Berg, Mark M. Davis, and colleauges demonstrate that a T cell receptot (TCR) binds to antagonist ligands with lower affinities and faster dissociation rates than to agonists.



Lyons DS, Lieberman SA, Hampl J, Boniface JJ, Chien Y-h, Berg LJ, Davis MM. A TCR binds to antagonist ligands with lower affinities and faster dissociation rates than to agonists. Immunity 1996 Jul; 5: 53-61. (PMID: 8758894)

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1996
Major Discovery
NEW DISCOVERY ON IL-2
Details
November 10, 1996
Major Discovery
NEW DISCOVERY ON IL-2

1996-Ellen-V-Rothenberg.jpgEllen V. Rothenberg and Susan B. Ward report that the interleukin-2 (IL-2) transcriptional apparatus integrates multiple types of biochemical information in determining whether or not the gene will be expressed, using multiple diverse transcription factors that are each optimally activated or inhibited by different signaling pathways.
 



Rothenberg EV, Ward SB. A dynamic assembly of diverse transcription factors integrates activation and cell-type information for interleukin 2 gene regulation. Proc Natl Acad Sci U S A 1996; 93: 9358-9365. (PMID: 8790334) Download PDF

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1996
Major Discovery
NEW DISCOVERY ON FCGRIII
Details
November 10, 1996
Major Discovery
NEW DISCOVERY ON FCGRIII

1996-Jeffrey-V-Ravetch.jpgDiana L. Sylvestre and Jeffrey V. Ravetch demonstrate by differential reconstitution in vivo that FcgRIII on mast cells is necessary for the inflammatory response to experimental immune complexes.


Sylvestre DL, Ravetch JV. A dominant role for mast cell Fc receptors in the Arthus reaction. Immunity 1996; 5: 387-390

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1996
Major Discovery
NEW FINDINGS ON TRANSCRIPTION FACTOR NFAT1
Details
November 10, 1996
Major Discovery
NEW FINDINGS ON TRANSCRIPTION FACTOR NFAT1

1996-Anjano-Rao.jpgAnjano Rao and colleagues find evidence in mice that transcription factor NFAT1 exerts a negative regulatory influence on the immune response.



Xanthoudakis S, Viola JPB, Shaw KTY, Luo C, Wallace JD, Bozza PT, Curran T, Rao A. An enhanced immune response in mice lacking the transcription factor NFAT1. Science 1996; 272: 892-895. (PMID: 8629027)

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1996
Major Discovery
CAUSE OF REJECTION OF TUMORS FOUND
Details
November 10, 1996
Major Discovery
CAUSE OF REJECTION OF TUMORS FOUND

James P. Allison and Matthew Krummel demonstrate that a monoclonal antibody directed against the CTLA-4 molecule in a mouse model of melanoma could result in the rejection of tumors and that this rejection also resulted in immunity to a second exposure to tumor cells.



Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996 Mar 22; 271: 1734-1736. (PMID: 8596936)

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1996
Major Discovery
FUNCTION OF TOLL RECEPTORS IN DROSOPHILA DISCOVERED
Details
November 10, 1996
Major Discovery
FUNCTION OF TOLL RECEPTORS IN DROSOPHILA DISCOVERED

1996-Toll-receptors-in-Drosophila.jpgBruno Lemaitre and Jules A. Hoffmann demonstrate that Toll receptors in Drosophila mediate immune defense against fungal infection.
 



Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 1996 Sep 20; 86: 973-983. (PMID: 8808632)

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1996
Major Discovery
DISCOVERIES ON IG GENE TRANSCRIPTION
Details
November 10, 1996
Major Discovery
DISCOVERIES ON IG GENE TRANSCRIPTION

Andy Peters and Ursula Storb show that the initiation of Ig gene transcription targets Ig gene somatic hypermutation (SHM), by duplicating the variable (V) region promoter upstream of the constant (C) region and showing that a second wave of mutations occurs over the C region. This finding led them to propose a novel hypothesis of SHM, namely that a mutator factor (now known to be AID) loads on the transcription complex near the promoter, travels with the elongating RNA polymerase, and stochastically dissociates, thus limiting SHM to the VJ region.



Peters A, Storb U. Somatic hypermutation of immunoglobulin genes is linked to transcription initiation. Immunity 1996 Jan; 4: 57-65. (PMID: 8574852)

Storb U. Progress in understanding the mechanism of somatic hypermutation. Immunol Rev 1998 Apr; 162: 5-11. (PMID: 9602347)

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1996
Major Discovery
DEMONSTRATION OF ENCHANCED IMMUNE RESPONSES
Details
November 10, 1996
Major Discovery
DEMONSTRATION OF ENCHANCED IMMUNE RESPONSES

Researchers in Frankfurt, including Elke Jaeger, Dirk Jaeger, Julia Karbach, and Alex Knuth demonstrate enchanced immune responses, including delayed type hypersensitivity, with GM-CSF as an adjuvant.



Jäger E, Ringhoffer M, Dienes HP, Arand M, Karbach J, Jäger D, Ilsemann C, Hagedorn M, Oesch F, Knuth A. Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo. Int J Cancer 1996 Jul 3; 67: 54-62. (PMID: 8690525)

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1996
Major Discovery
DISCOVERY ON ANTIGEN-SPECIFIC CD4+ T CELLS DURING TUMOR GROWTH
Details
November 10, 1996
Major Discovery
DISCOVERY ON ANTIGEN-SPECIFIC CD4+ T CELLS DURING TUMOR GROWTH

1996-Bjarne-Bogen.jpgBjarne Bogen provides experimental evidence that antigen-specific CD4+ T cells are rendered tolerant during tumor growth in vivo.



Bogen B. Peripheral T cell tolerance as a tumor escape mechanism: deletion of CD4+ T cells specific for a monoclonal immunoglobulin idiotype secreted by a plasmacytoma. Eur J Immunol 1996 Nov; 26: 2671-2679. (PMID: 8921954)

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1996
Major Discovery
THE FIRST SIGNIFICANT IMPROVEMENT FOR MELANOMA PATIENTS REPORTED
Details
November 10, 1996
Major Discovery
THE FIRST SIGNIFICANT IMPROVEMENT FOR MELANOMA PATIENTS REPORTED

2001-John-M-Kirkwood.jpgJohn M. Kirkwood reports the first significant improvement of both survival and relapse-free interval for melanoma patients treated with high-dose Interferon alfa-2b (E1684).

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1995
Major Discovery
NEW DISCOVERY ON REGULATORY T CELLS (CD4+CD25+)
Details
November 10, 1995
Major Discovery
NEW DISCOVERY ON REGULATORY T CELLS (CD4+CD25+)

1995-Shimon-Sakaguchi.jpgShimon Sakaguchi identifies regulatory T cells (CD4+CD25+) and their role in protecting against autoimmunity.



Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995 Aug 1; 155: 1151-1164. (PMID: 7636184) Download PDF

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1995
Tools & Technologies
SEREX DEVELOPED
Details
November 10, 1995
Tools & Technologies
SEREX DEVELOPED

Michael Pfreundschuh and colleagues Ugur Sahin and Ozlem Türeci at the University of Saarland develop SEREX (SErological analysis of Recombinant cDNA Expression), providing a powerful method to analyze the humoral immune response to intracellular cancer antigens and ushering in the third phase of cancer serology, bringing with it the prospect of providing a comprehensive view of the immune recognition of human cancer.
 



Sahin U, Tureci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfeundschuh M. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A 1995 Dec 5; 92: 11810-11813. (PMID: 8524854) Download PDF

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1995
Major Discovery
DISCOVERY OF SLP-76
Details
November 10, 1995
Major Discovery
DISCOVERY OF SLP-76

1995-Gary-Koretsky.jpgGary Koretsky and colleagues report the discovery of SLP-76.
 



Jackman JK, Motto DG, Sun Q, Tanemoto M, Turck CW, Peltz GA, Koretzky GA, Findell PR. Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated with Grb2 in T cells. J Biol Chem 1995 Mar 31; 270: 7029. (PMID: 7706237) Download PDF

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1995
Major Discovery
FIRST CASES OF CLINICAL REGRESSIONS OF MELANOMA METASTASES REPORTED
Details
November 10, 1995
Major Discovery
FIRST CASES OF CLINICAL REGRESSIONS OF MELANOMA METASTASES REPORTED

Marie Marchand and Thierry Boon report the first cases of clinical regressions of melanoma metastases following vaccination with a MAGE-A3 peptide.[i] Additional cases will be reported in 1999, confirming these promising clinical results.[ii]


[i] Marchand M, Weynants P, Rankin E, Arienti F, Belli F, Parmiani G, Cascinelli N, Bourlond A, Vanwijck R, Humblet Y, Canon J-L, Laurent C, Naeyaert J-M, Plagne R, Deraemaeker R, Knuth A, Jäger E, Brasseur F, Herman J, Coulie PG, Boon T. Tumor regression responses in melanoma patients treated with a peptide encoded by gene MAGE-3. Int J Cancer 1995 Dec 11; 63: 883-885. (PMID: 8847150)

[ii] Marchand M, van Baren N, Weynants P, Brichard V, Dréno B, Tessier M-H, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Liénard D, Beauduin M, Dietrich P-Y, Russo V, Kerger J, Masucci G, Jäger E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van der Bruggen P, Boon T. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer 1999 Jan 18; 80: 219-230. (PMID: 9935203)

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1995
Major Discovery
NEW DISCOVERY ON HUMAN T LYMPHOCYTES
Details
November 10, 1995
Major Discovery
NEW DISCOVERY ON HUMAN T LYMPHOCYTES

1995-new-discovery-on-human-T-lymphocytes.jpgPierre Coulie and Thierry Boon,[i] and Thomas Wölfel[ii] show that human T lymphocytes recognize antigens caused by driver278 or passenger279 tumor-specific mutations.
 



[i] Coulie PG, Lehmann F, Lethé B, Herman J, Lurquin C, Andrawiss M, Boon T. A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma. Proc Natl Acad Sci U S A 1995 Aug 15; 92: 7976-7980. (PMID: 7644523) Download PDF

[ii] Wölfel T, Hauer M, Schneider J, Serrano M, Wölfel C, Klehmann-Hieb E, De Plaen E, Hankeln T, Meyer zum Büschenfelde K-H, Beach D. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 1995 Sep 1; 269: 1281-1284. (PMID: 7652577)

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1995
Major Discovery
NEW FINDINGS ON CPG OLIGONUCLEOTIDES
Details
November 10, 1995
Major Discovery
NEW FINDINGS ON CPG OLIGONUCLEOTIDES

Arthur M. Krieg and coworkers characterize CpG oligonucleotides and discover that they are robust stimulators of immune cells. CpG oligonucleotides are TLR9 agonists and have broad therapeutic application in humans.
 



Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995 Apr 6; 374: 546-549. (PMID: 7700380)

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1995
Major Discovery
THE ROLE FOR JAK-STAT DISCOVERED
Details
November 10, 1995
Major Discovery
THE ROLE FOR JAK-STAT DISCOVERED

1995-Paul-Rothman.jpgPaul Rothman demonstrates a role for JAK-STAT signaling in malignancy.



Danial N, Pernis A, Rothman P. Jak-STAT signaling induced by the v-abl oncogene. Science 1995 Sep 29; 269:1875-1877. (PMID: 7569929)

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1995
Treatment Approved
TRETINOIN APPROVED BY FDA
Details
November 10, 1995
Treatment Approved
TRETINOIN APPROVED BY FDA

The FDA approves tretinoin, a differentiating agent related to vitamin A, for use in the treatment of acute promyelocytic leukemia. Tretinoin is also known as all-trans retinoic acid (ATRA). (NCI)

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1995
Awards & Honors
CRI ANNOUNCED ITS 1995 COLEY AWARD
Details
November 10, 1995
Awards & Honors
CRI ANNOUNCED ITS 1995 COLEY AWARD

CRI presents the 1995 Coley Award to Ferdy J. Lejeune, Malcolm A.S. Moore, and Timothy Springer.

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1995
Major Discovery
FIRST REPORT ON DENDRITIC CELL VACCINATION FOR CANCER
Details
November 10, 1995
Major Discovery
FIRST REPORT ON DENDRITIC CELL VACCINATION FOR CANCER

Bijay Mukherji and colleagues provide the first report on dendritic cell vaccination for cancer.



Mukherji B, Chakraborty NG, Yamasaki S, Okino T, Yamase H, Sporn JR, Kurtzman SK, Ergin MT, Ozols J, Meehan J, Mauri F. Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. Proc Natl Acad Sci U S A 1995 Aug 15; 92: 8078-8082. (PMID: 7644541) Download PDF

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1994
Major Discovery
NKT CELL DISCOVERED
Details
November 10, 1994
Major Discovery
NKT CELL DISCOVERED

1995-Albert-Bendelac.jpgAlbert Bendelac discovers and characterizes the natural killer T (NKT) cell.
 



Bendelac A, Killeen N, Littman DR, Schwartz RH. A subset of CD4+ thymocytes selected by MHC class I molecules. Science 1994 Mar 25; 263: 1774-1778. (PMID: 7907820) Bendelac A, Lantz O, Quimby E, Yewdell JW, Bennink JR, Brutkiewicz RR. CD1 recognition by mouse NK1+ T lymphocytes. Science 1995 May 12; 268: 863-865. (PMID: 7538697)

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1994
Major Discovery
IDENTIFICATION OF SEVERAL FAMILIES OF CANCER-GERMLINE GENES
Details
November 10, 1994
Major Discovery
IDENTIFICATION OF SEVERAL FAMILIES OF CANCER-GERMLINE GENES

Several families of cancer-germline genes are identified by the group of Thierry Boon, including the MAGE,[i] BAGE,[ii] and GAGE[iii] families. These genes are expressed in many tumors and are silent in normal tissues except male germline cells. Many of them encode tumor-specific antigens recognized by T lymphocytes.
 



[i] De Plaen E, Arden K, Traversari C, Gaforio JJ, Szikora J-P, De Smet C, Brasseur F, van der Bruggen P, Lethé B, Lurquin C, Brasseur R, Chomez P, De Backer O, Cavenee W, Boon T. Structure, chromosomal localization, and expression of 12 genes of the MAGE family. Immunogenetics 1994; 40: 360-369. (PMID: 7927540)

[ii] Boël P, Wildmann C, Sensi M-L, Brasseur R, Renauld J-C, Coulie P, Boon T, van der Bruggen P. BAGE, a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 1995 Feb; 2: 167-175. (PMID: 7895173)

[iii] Van den Eynde B, Peeters O, De Backer O, Gaugler B, Lucas S, Boon T. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med 1995 Sep 1; 182: 689-698. (PMID: 7544395) Download PDF

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1994
Major Discovery
NEW DISCOVERY ON INTERFERON
Details
November 10, 1994
Major Discovery
NEW DISCOVERY ON INTERFERON

1994-James-Darnell.jpgJames Darnell, George Stark, and Ian Kerr report studies demonstrating the importance of interferon to elucidate signal trafficking from the cell surface to the nucleus.
 



Darnell JE, Kerr IM, Stark GR. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994 Jun 3; 264: 1415. (PMID: 8197455)

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1994
Major Discovery
CTLA-4 AS NEGATIVE REGULATOR OF T CELL ACTIVATION DEMONSTRATED
Details
November 10, 1994
Major Discovery
CTLA-4 AS NEGATIVE REGULATOR OF T CELL ACTIVATION DEMONSTRATED

1994-CTLA-4.pngAkiko Uenaka and Eiichi Nakayama identify a murine leukemia antigen recognized by cytotoxic T cells.



Uenaka A, Ono T, Akisawa T, Wada H, Yasuda T, Nakayama E. Identification of a unique antigen peptide pRL1 on BALB/c RL male 1 leukemia recognized by cytotoxic T lymphocytes and its relation to the Akt oncogene. J Exp Med 1994 Nov 1; 180: 1599-1607. (PMID: 7964448) Download PDF

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1994
Major Discovery
HHV-8 IDENTIFIED
Details
November 10, 1994
Major Discovery
HHV-8 IDENTIFIED

1994-HHV-8-identified.jpgHuman herpesvirus 8 (HHV-8), which causes Kaposi’s sarcoma, is identified.

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1994
Field Milestone
‘DANGER’ MODEL OF IMMUNOLOGICAL TOLERANCE PROPOSED
Details
November 10, 1994
Field Milestone
‘DANGER’ MODEL OF IMMUNOLOGICAL TOLERANCE PROPOSED

1994-Polly-Matzinger.jpgPolly Matzinger proposes the ‘danger’ model of immunological tolerance.
 



Matzinger P. Tolerance, danger, and the extended family. Ann Rev Immunol 1994; 12: 991-1045. (PMID: 8011301)

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1994
Major Discovery
DISCOVERY ON GENE MAGE-A3
Details
November 10, 1994
Major Discovery
DISCOVERY ON GENE MAGE-A3

1994-Benoit-Van-den-Eynde-1.jpgBenoit Van den Eynde, Pierre van der Bruggen, Béatrice Gaugler, and Thierry Boon identify gene MAGE-A3 as encoding a peptide recognized by melanoma-specific CTL. Being both tumor-specific and widely expressed in human tumors, MAGE-A3 is an ideal cancer vaccine target and will be the focus of many clinical trials, including the largest clinical trial ever conducted in lung cancer, MAGRIT, launched by GlaxoSmithKline in 2007.
 



Gaugler B, Van den Eynde B, van der Bruggen P, Romero P, Gaforio JJ, De Plaen E, Lethé B, Brasseur F, Boon T. Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. J Exp Med 1994 Mar 1; 179: 921-930. (PMID: 8113684) Download PDF

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1994
Major Discovery
DISCOVERY ON TUMOR-ASSOCIATED ANTIGEN
Details
November 10, 1994
Major Discovery
DISCOVERY ON TUMOR-ASSOCIATED ANTIGEN

1994-Alex-Huang.jpgAlex Huang and Drew Pardoll, with Elizabeth Jaffee and Hyam Levitsky at Johns Hopkins School of Medicine demonstrate tumor-associated antigen processing and presentation to CD8+ T cell by bone marrow-derived professional antigen presenting cells via “cross-priming.”



Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 1994 May 13; 264: 961-965. (PMID: 7513904)

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1994
Major Discovery
PDC SUBSET IN CIRCULATING BLOOD DISCOVERED
Details
November 10, 1994
Major Discovery
PDC SUBSET IN CIRCULATING BLOOD DISCOVERED

Ralph Steinman and Nina Bhardwaj, independently with other laboratories, discover the plasmacytoid dendritic cell (pDC) subset in circulating blood.



O’Doherty U, Peng M, Gezelter S, Swiggard WJ, Betjes M, Bhardwaj N, Steinman RM. Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature. Immunology 1994 Jul; 82: 487-493. (PMID:7525461) Download PDF

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1994
Major Discovery
DISCOVERY ON A NEW MEMBER OF THE JAK-3
Details
November 10, 1994
Major Discovery
DISCOVERY ON A NEW MEMBER OF THE JAK-3

1994-John-J-O’Shea.jpgJohn J. O’Shea and colleagues report that a new member of the Janus family of kinases (JAK-3) is coupled to the interleukin 2 receptor (IL-2R) in human peripheral blood T cells and natural killer cells. Interaction with interleukin 2 (IL-2) leads to the phosphorylation and activation of JAK-3.



Johnston JA, Kawamura M, Kirken RA, Chen Y-Q, Blake TB, Shibuya K, Ortaldo JR, McVicar DW, O'Shea JJ. 1994. Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2. Nature 370: 151-3.

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1994
Major Discovery
DISCOVERY OF MOBILIZATION OF LARGE NUMBERS OF DENDRITIC CELLS
Details
November 10, 1994
Major Discovery
DISCOVERY OF MOBILIZATION OF LARGE NUMBERS OF DENDRITIC CELLS

1994-Gerold-Schuler.jpgRalph M. Steinman, Gerold Schuler, and colleagues find that large numbers of dendritic cells can be mobilized by specific cytokines from progenitors in the blood stream.
 



Romani N, Gruner S, Brang D, Kampgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM, Schuler G. Proliferating dentritic cell progenitors in human blood. J Exp Med 1994; 180: 83-93. (PMID: 8006603)

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1994
Major Discovery
NEW FINDINGS ON THE EFFICIENT PRESENTATION OF SOLUBLE ANTIGEN
Details
November 10, 1994
Major Discovery
NEW FINDINGS ON THE EFFICIENT PRESENTATION OF SOLUBLE ANTIGEN

1994-Antonio-Lanzavecchia.jpgAntonio Lanzavecchia finds that efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.



Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 1974 Apr 1; 179: 1109-1118. (PMID: 8145033) Download PDF

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1994
Major Discovery
NEW FINDINGS ON A MURINE STRAIN DEFICIENT IN FC RECEPTOR EXPRESSION
Details
November 10, 1994
Major Discovery
NEW FINDINGS ON A MURINE STRAIN DEFICIENT IN FC RECEPTOR EXPRESSION

Diana L. Sylvestre and Jeffrey V. Ravetch find a murine strain deficient in Fc receptor expression could respond normally to other stimuli yet their inflammatory response to immune complexes was markedly attenuated. These results suggest that immune complex-triggered inflammation is initiated by cell bound Fc receptors and is then amplified by cellular mediators and activated complement.


Sylvestre DL, Ravetch JV. Fc receptors initiate the Arthus reaction: Redefining the inflammatory cascade. Science 1994 Aug 19; 265: 1095-1098. (PMID: 8066448)

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1994
Major Discovery
FIRST DEMONSTRATION ON TREATMENT WITH MONOCLONAL ANTIBODIES
Details
November 10, 1994
Major Discovery
FIRST DEMONSTRATION ON TREATMENT WITH MONOCLONAL ANTIBODIES

Alan Houghton, Carl F. Nathan, and colleagues provide the first demonstration that treatment with monoclonal antibodies can lead to reproducible tumor responses in cancer patients with solid tumors.



Minasian LM, Szatrowski TP, Rosenblum M, Steffens T, Morrison ME, Chapman PB, Williams L, Nathan CF, Houghton AN. Hemorrhagic tumor necrosis during a pilot trial of tumor necrosis factor-alpha and anti-GD3 ganglioside monoclonal antibody in patients with metastatic melanoma. Blood 1994 Jan 1; 83: 56-64. (PMID: 8274754) Download PDF

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1993
Major Discovery
DISCOVERY ON HUMAN CLASS II MHC
Details
November 10, 1993
Major Discovery
DISCOVERY ON HUMAN CLASS II MHC

1993-Theodore-S-Jardetzky.jpgTheodore S. Jardetzky is part of the team that identifies the three-dimensional crystal structure of the human class II major histocompatibility complex (MHC) in the presence of superantigen.
 



Brown JH, Jardetsky TS, Gorga JC, Stern LJ, Urban R, Strominger JL, Wiley DC. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 1993 Jul 1; 364: 33-39. (PMID: 8316295)

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1993
Major Discovery
DISCOVERY ON THERAPEUTIC CANCER VACCINE GVAX
Details
November 10, 1993
Major Discovery
DISCOVERY ON THERAPEUTIC CANCER VACCINE GVAX

1993-Drew-Pardoll.jpgDrew Pardoll, Glenn Dranoff, Elizabeth Jaffee, Hyam Levitsky, and colleagues conduct preclinical studies showing that a vaccine composed of tumor cells irradiated and genetically modified to produce immune system growth factor GM-CSF (granulocyte-macrophage colony-stimulating factor)—which would become known as the therapeutic cancer vaccine GVAX—could induce potent, specific, and long-lasting anti-tumor immunity in multiple mouse tumor models. Based on these preclinical findings, CRI provides a seed grant for a phase I clinical trial to test the strategy in patients with metastatic renal cell carcinoma. “When I began my career in cancer research in 1989, CRI was the only organization that believed in supporting junior researchers as the future of cancer immunotherapy. I had just had my NIH grant turned down and CRI gave me an investigators grant that allowed me to launch my career. They then funded a number of postdoctoral fellows, who are now themselves independent cancer immunology leaders at institutions all over the world. Without CRI, I would not be doing this today. Starting in 2010, cancer immunotherapy has emerged as the "new" breakthrough approach to cancer therapy but this is actually the fruit of decades of labor and CRI has been steadfastly behind that research from the beginning.” – Drew Pardoll


Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, and Mulligan RC. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A 1993 Apr 15; 90: 3539-3543. (PMID: 8097319). Download PDF

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1993
Major Discovery
DISCOVERY ON HUMAN MELANOMA ANTIGENS
Details
November 10, 1993
Major Discovery
DISCOVERY ON HUMAN MELANOMA ANTIGENS

1993-Giorgio-Parmiani.jpgGiorgio Parmiani and colleagues are the first to unequivocally demonstrate that human melanoma antigens recognized by patient T cells include molecules belonging to the normal melanocyte lineage. These antigens were molecularly defined the following year both by Steve A. Rosenberg (named MART-1) at the National Cancer Institute and Thierry Boon (named Melan-A) at the LICR Brussels Branch. The discovery that lineage-related melanoma antigens can be recognized by patients’ T cells then opened the way to their use in melanoma immunotherapy.


Anichini A, Maccalli C, Mortarini R, Salvi S, Mazzocchi A, Squarcina P, Herlyn M, Parmiani G. Melanoma cells and normal melanocytes share antigens recognized by HLA-A2-restricted cytotoxic T cell clones from melanoma patients. J Exp Med 1993 Apr 1; 177: 989-998. (PMID: 8459226) Download PDF

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1993
Major Discovery
MOLECULAR IDENTIFICATION OF THE TRANSCRIPTION FACTOR NFAT REPORTED
Details
November 10, 1993
Major Discovery
MOLECULAR IDENTIFICATION OF THE TRANSCRIPTION FACTOR NFAT REPORTED

Anjana Rao and colleagues Jugnu Jain, Patricia McCaffrey, and Patrick Hogan report the molecular identification of the transcription factor NFAT (nuclear factor of activated T cells). They show that it is a substrate for calcineurin, the phosphatase target of the immunosuppressive drugs cyclosporin A and FK506, and that it exists in activated cells as a complex with the transcription factor AP-1 (Fos-Jun). [i] Gerald Crabtree had earlier described NFAT as an inducible, cyclosporine-sensitive DNA-binding activity in 1988.[ii]
 



[i] Jain J, McCaffrey PG, Miner Z, Kerppola TK, Lambert JN, Verdine GL, Curran T, Rao A. The T cell transcription factor NFATp is a substrate for calcineurin and interacts with the DNA-binding domains of Fos and Jun. Nature 1993; 365: 352-355. (PMID: 8397339)

McCaffrey PG, Luo C, Kerppola TK, Jain J, Badalian TM, Ho AM, Burgeon E, Lane WS, Lambert JL, Curran T, Verdine GL, Rao A, Hogan PG. Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science 1993 Oct 29; 262: 750-754. (PMID: 8235597)

[ii] Shaw JP, Utz PJ, Durand DB, Toole JJ, Emmel EA, Crabtree GR. Identification of a putative regulator of early T cell activation genes. Science 1988 Jul 8; 241: 202-205. (PMID: 3260404) Download PDF

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1993
Major Discovery
DISCOVERY ON TH1 DEVELOPMENT OF CD4+ T CELLS
Details
November 10, 1993
Major Discovery
DISCOVERY ON TH1 DEVELOPMENT OF CD4+ T CELLS

1993-Kenneth-M-Murphy.jpgKenneth M. Murphy and Anne O’Garra discover that dendritic cells and macrophages are required for T-helper 1(Th1) development of CD4+ T cells. They also determine that interleukin 12 (IL-12) substitution for macrophages to stimulate IFN-gamma production is IFN-gamma-dependent.
 



Macatonia SE, Hsieh C-S, Murphy KM, O'Garra A. Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from alpha beta TCR transgenic mice IL-12 substitution for macrophages to stimulate IFN-gamma production is IFN-gammadependent. International Immunology 1993; 5: 1119-1128.

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1993
Major Discovery
THE FIRST CTL-DEFINED TUMOR ANTIGEN DERIVED FROM TYROSINASE IDENTIFIED
Details
November 10, 1993
Major Discovery
THE FIRST CTL-DEFINED TUMOR ANTIGEN DERIVED FROM TYROSINASE IDENTIFIED

Vincent Brichard, Thomas Wölfel, and Thierry Boon identify the first CTL-defined tumor antigen derived from a melanoma differentiation protein, tyrosinase. [i] Other examples were later identified by Pierre Coulie and Thierry Boon[ii] and by Yutaka Kawakami and Steven Rosenberg.[iii]
 



[i] Brichard V, Van Pel A, Wölfel T, Wölfel C, De Plaen E, Lethé B, Coulie P, Boon T. The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 1993 Aug 1; 178: 489-495. (PMID: 8340755) Download PDF

Wölfel T, Hauer M, Klehmann E, Brichard V, Ackermann B, Knuth A, Boon T, Meyer zum Büschenfelde K-H. Analysis of antigens recognized on human melanoma cells by A2-restricted cytolytic T lymphocytes (CTL). Int J Cancer 1993 Sep 9; 55: 237-244. (PMID: 7690346)

[ii] Coulie PG, Brichard V, Van Pel A, Wölfel T, Schneider J, Traversari C, Mattei S, De Plaen E, Lurquin C, Szikora J-P, Renauld J-C, Boon T. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 1994 Jul 1; 180: 35-42. (PMID: 8006593) Download PDF

[iii] Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A 1994 Apr 26; 91: 3515-3519. (PMID: 8170938) Download PDF

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1993
Major Discovery
IDENTIFICATION OF THE FIRST INHIBITORY RECEPTORS
Details
November 10, 1993
Major Discovery
IDENTIFICATION OF THE FIRST INHIBITORY RECEPTORS

Lorenzo Moretta and colleagues report on the identification of the first inhibitory receptors on human natural killer cells.



Moretta A, Vitale M, Bottino C, Orengo AM, Morelli L, Augugliaro R, Barbaresi M, Ciccone E, Moretta L. P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells: anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities. J Exp Med 1993 Aug 1; 178: 597-604. (PMID: 8340759) Download PDF

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1993
Field Milestone
DISCOVERY OF THE ROLE OF HEAT-SHOCK PROTEINS IN TUMOR IMMUNITY
Details
November 10, 1993
Field Milestone
DISCOVERY OF THE ROLE OF HEAT-SHOCK PROTEINS IN TUMOR IMMUNITY

1984-Pramod-Srivastava-1.jpgPramod K. Srivastava demonstrates the role of heat-shock proteins in tumor immunity and forms the company Antigenics (now Agenus) to explore their potential in cancer vaccines.

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1993
Tools & Technologies
XENOMOUSE CREATED
Details
November 10, 1993
Tools & Technologies
XENOMOUSE CREATED

1993-Aya-Jakobovits.JPGAya Jakobovits and colleagues at Cell Genesys create the XenoMouse, the first mouse strain engineered to produce fully humanized monoclonal antibodies.



Jakobovits A, Vergara GJ, Kennedy JL, Hales JF, McGuinness RP, Casentini-Borocz DE, Brenner DG, Otten GR. Analysis of homozygous mutant chimeric mice: deletion of the immunoglobulin heavy-chain joining region blocks B-cell development and antibody production. Proc Natl Acad Sci U S A 1993 Mar 15; 90: 2551-2555. (PMID: 8460171) Download PDF

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1993
Awards & Honors
CRI ANNOUNCED ITS 1993 COLEY AWARD
Details
November 10, 1993
Awards & Honors
CRI ANNOUNCED ITS 1993 COLEY AWARD

CRI presents the 1993 Coley Award to Pamela Bjorkman, Jack Strominger, and Don Wiley for solving the structure of the MHC-antigen complex; to John Kappler and Philippa Marrack for the isolation of the T cell receptor; and to Alvaro Morales for establishing the effectiveness of BCG in the treatment of superficial bladder cancer.

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1993
Field Milestone
P53 NAMED “MOLECULE OF THE YEAR”
Details
November 10, 1993
Field Milestone
P53 NAMED “MOLECULE OF THE YEAR”

1993-Molecule-of-the-Year.pngScience names p53 “Molecule of the Year.”

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1992
Major Discovery
FIRST CHARACTERIZATION OF PEPTIDES REPORTED
Details
November 10, 1992
Major Discovery
FIRST CHARACTERIZATION OF PEPTIDES REPORTED

1993-Don-Hunt.jpgDon Hunt and Victor Engelhard report the first characterization of peptides from an MHC class I molecule by mass spectrometry.



Hunt DF, Henderson RA, Shabanowitz J, Sakaguchi K, Michel H, Sevilir N, Cox AL, Appella E, Engelhard VH. Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry. Science 1992 Mar 6; 255: 1261-1263. (PMID: 1546328) Download PDF

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1992
Field Milestone
THE CDC DEFINES AIDS
Details
November 10, 1992
Field Milestone
THE CDC DEFINES AIDS

1993-CDC.jpgThe CDC rules that a cell count of less than 200 CD4 (T4) cells/mm3 combined with an HIV-positive status defines AIDS.

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1992
Field Milestone
INTERNATIONAL CYTOKINE SOCIETY FOUNDED
Details
November 10, 1992
Field Milestone
INTERNATIONAL CYTOKINE SOCIETY FOUNDED

1993-International-Cytokine-Society-founded_1.jpgThe International Cytokine Society is founded.



“Cytokines provide the intercellular communication links between the immune system and other tissues and organs…Thus, the study of cytokines has helped to propel immunology from the limited areas of immunological specificity to larger concerns of the cell biology, biochemical, molecular, and clinical aspects of host defense.”

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1992
CRI Milestone
CRI'S INTERNATIONAL SYMPOSIA SERIES INAUGURATED
Details
November 10, 1992
CRI Milestone
CRI'S INTERNATIONAL SYMPOSIA SERIES INAUGURATED

CRI inaugurates its international symposia series with a meeting on Frontiers of Immunology and Cancer Immunology, dedicated to Dr. William B. Coley and commemorating his first clinical use of bacterial vaccines to treat cancer. The symposium features presentations by Philippa Marrack and John Kappler talking on the T cell repertoire; William Paul on interleukin 4 as a prototypic immunoregulatory cytokine; Timothy Springer on lymphocyte trafficking; Pamela Bjorkman on structural studies of MHC and MHC-related proteins, and Jack Strominger on peptide presentation by class I and II MHC proteins; Thierry Boon on genes coding for tumor rejection antigens, including the first tumor antigen, MAGE-1; and Philip Greenberg on the modification of T cells for adoptive therapy by retroviral-mediated gene insertion Since then, the symposia series has attracted leading immunologists in the cancer vaccine and antibody fields, providing them with a comprehensive view of the promises and challenges in the development of cancer immunotherapies.

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1992
Major Discovery
TAP CRITICAL IN CLASS I-RESTRICTED ANTIGEN PRESENTATION
Details
November 10, 1992
Major Discovery
TAP CRITICAL IN CLASS I-RESTRICTED ANTIGEN PRESENTATION

Luc Van Kaer, with Hidde Ploegh and sponsor Susumu Tonegawa, demonstrates a critical role of the TAP pathway for class I-restricted antigen presentation in vivo.”

Van Kaer L, Ashton-Richardt PG, Ploegh HL, Tonegawa S. TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4-8+ T cells. Cell 1992 Dec 24; 71: 1205-1214. (PMID: 1473153)

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1992
Major Discovery
ZAP-70 DISCOVERED
Details
November 10, 1992
Major Discovery
ZAP-70 DISCOVERED

Arthur Weiss and colleagues report the discovery of ZAP-70 and its association with the T cell receptor following activation.

Chan AC, Iwashima M, Trck CW, Weiss A. ZAP-70: a 70kd protein-tyrosine kinase that associates with the TCRzeta chain. Cell 1992 Nov 13; 71: 649-662. (PMID: 1423621)

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1992
Major Discovery
THE FIRST STUDY OF ISOLATED LIMB PERFUSION IN PATIENTS WITH MELANOMA AND SARCOMA
Details
November 10, 1992
Major Discovery
THE FIRST STUDY OF ISOLATED LIMB PERFUSION IN PATIENTS WITH MELANOMA AND SARCOMA

1992-Ferdy-Lejeune.jpgFerdy Lejeune and colleagues report the first study of isolated limb perfusion with tumor necrosis factor in patients with melanoma and sarcoma.



Lienard D, Ewalenko P, Delmotte JJ, Renard N, and Lejeune FJ. High-dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma. J Clin Oncol 1992 Jan; 10: 52-60. (PMID: 1727926)

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1992
Tools & Technologies
TNF RELEASE ASSAY FOR MOUSE SYSTEMS DEVELOPED
Details
November 10, 1992
Tools & Technologies
TNF RELEASE ASSAY FOR MOUSE SYSTEMS DEVELOPED

Lloyd Old, Thierry Boon, and colleagues develop the TNF release assay for mouse systems in which release of TNF by T cells could be used to assess specific T cell recognition, facilitating the cloning of human tumor antigens.


Traversari C, van der Bruggen P, Van den Eynde B, Hainaut P, Lemoine C, Ohta N, Old L J, Boon T. Transfection and expression of a gene coding for a human melanoma antigen recognized by autologous cytolytic T lymphocytes. Immunogenetics 1992; 35: 145-152. (PMID:1537606)

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1992
Major Discovery
DISCOVERIES ON STAT GENE FAMILY
Details
November 10, 1992
Major Discovery
DISCOVERIES ON STAT GENE FAMILY

1992-Xin-Yuan-Fu.jpgXin-Yuan Fu and James E. Darnell, Jr. report the discovery of the STAT gene family and the cloning of the first two STAT family members (STAT1 and STAT2). The discovery of the STAT pathway was cited as one of the 10 major breakthroughs of the year by Science, and the STAT pathway is known now as a major pathway involved in immunity control, development, and cancer pathogenesis. 



Fu X-Y, Schindler C, Improta T, Aebersold R, Darnell JE. The proteins of ISGF3, the IFN-alpha induced transcriptional activator, define a gene family involved in signal transdution. Proc Natl Acad Sci U S A 1992 Aug 15; 89: 7840-7843. (PMID: 1502204) Download PDF
 

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1992
Major Discovery
DISCOVERY ON CD28 AND T CELL ACTIVATION
Details
November 10, 1992
Major Discovery
DISCOVERY ON CD28 AND T CELL ACTIVATION

James Allison and David Raulet (also Jane A. Gross, 1991-1994 CRI Fellow with Roger Perlmutter) demonstrate that blocking CD28 hampers T cell activation by antigen presenting cells and antigen.



Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. CD28-mediated signaling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 1992 Apr 16; 356: 607-609. (PMID: 1313950)

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1992
Major Discovery
FIRST DEMONSTRATION OF TOLERANCE INDUCTION BY COSTIMULATION BLOCKADE
Details
November 10, 1992
Major Discovery
FIRST DEMONSTRATION OF TOLERANCE INDUCTION BY COSTIMULATION BLOCKADE

1992-Jeffrey-Bluestone.jpgJeffrey Bluestone and colleagues provide the first demonstration of tolerance induction by costimulation blockade. These studies, showing the functional effects of CTLA-4 Ig as a potential tolerogen,[i] led to the discovery of CD86[ii] and the development of the first costimulation blockade (Abatecept).[iii]



[i] Lenschow DJ, Zeng Y, Thistlethwaite JR, Montag A, Brady W, Gibson MG, Linsley PS, Bluestone JA. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig. Science 1992 Aug 7; 257: 789-792. (PMID: 1323143)

[ii] Lenschow DJ, Su GH-T, Zuckerman LA, Nabavi N, Jellis CL, Gray GS, Miller J, Bluestone JA. Expression and functional significance of an additional ligand for CTLA-4. Proc Natl Acad Sci U S A1993 Dec 1; 90: 11054-11058. (PMID: 7504292) Download PDF

[iii] Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA. Anti-CD3 monoclonal antibody in new onset type 1 diabetes. N Eng J Med 2002 May 30; 346: 1692-1698. (PMID: 12037148) Download PDF
 

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1991
Treatment Approved
PACLITAXEL APPROVED BY THE FDA FOR THE TREATMENT OF ADVANCED OVARIAN CANCER
Details
November 10, 1991
Treatment Approved
PACLITAXEL APPROVED BY THE FDA FOR THE TREATMENT OF ADVANCED OVARIAN CANCER

1992-Paclitaxel.jpgPaclitaxel, the first of a class of drugs known as taxanes, is approved by the FDA for the treatment of advanced ovarian cancer.

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1980
1989
Major Discovery
CLONAL DELETION OF AUTOREACTIVE B CELLS DEMONSTRATED
Details
November 09, 1989
Major Discovery
CLONAL DELETION OF AUTOREACTIVE B CELLS DEMONSTRATED
David Nemazee and colleagues demonstrate clonal deletion of autoreactive B cells in a BCR transgenic model specific for MHC class I.
 

Nemazee DA, Bürki K. Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature 1989 Feb 9; 337: 562-566. (PMID: 2783762)
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1989
Major Discovery
CD4 PROVED TO BE COUPLED TO THE TYROSINE KINASE LCK
Details
November 09, 1989
Major Discovery
CD4 PROVED TO BE COUPLED TO THE TYROSINE KINASE LCK

1990-tyrosine-kinases.jpgLarry Samelson and colleagues demonstrate that CD4 is coupled to the tyrosine kinase LCK.
 



Veillette A, Bookman MA, Horak EM, Samelson LE, Bolen JB. Signal transduction through the T-lymphocyte CD4 receptor involves the activation of the internal membrane tyrosine-protein kinase p56lck. Nature 1989 Mar 16; 338: 257-259. (PMID: 2784195)
 

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1989
Major Discovery
THE ROLE OF CD28 IN T CELL COSTIMULATION DISCOVERED
Details
November 09, 1989
Major Discovery
THE ROLE OF CD28 IN T CELL COSTIMULATION DISCOVERED

1989-T-cell-costimulation.jpgCarl June, Craig B. Thompson, and colleagues demonstrate the role of CD28 in T cell costimulation.



Thompson CV, Lindsten T, Ledbetter JA, Kunkel SL, Young SA, Emerson SG, Leiden JM, June CL. CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. Proc Natl Acad Sci U S A 1989 Feb; 86: 1333-1337. (PMID: 2465550) Download PDF

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1989
Major Discovery
THE FIRST EVIDENCE FOR THE IMMUNE SURVEILLANCE OF THE INTEGRITY OF THE GENOME
Details
November 09, 1989
Major Discovery
THE FIRST EVIDENCE FOR THE IMMUNE SURVEILLANCE OF THE INTEGRITY OF THE GENOME
Thierry Boon and Etienne De Plaen clone the gene encoding the antigen recognized by CTL on mouse immunogenic mutagenized tum- variants, and show that the tum- antigen is created by a point mutation. With Christophe Lurquin, they further show that CTL recognize a peptide bearing the mutated residue. This was the first evidence for the immune surveillance of the integrity of the genome, leading to the concept that cells bearing mutations are immunogenic. This work also established the technology that was later used for the cloning of human tumor antigens recognized by CTL.
 

De Plaen E, Lurquin C, Van Pel A, Mariamé B, Szikora J-P, Wölfel T, Sibille C, Chomez P, Boon T. Immunogenic (tum-) variants of mouse tumor P815: cloning of the gene of tum- antigen P91A and identification of the tum- mutation. Proc Natl Acad Sci U S A 1988 Apr; 85: 2274-2278. (PMID: 3127830) Wölfel T, Van Pel A, De Plaen E, Lurquin C, Maryanski JL, Boon T. Immunogenic (tum-) variants obtained by mutagenesis of mouse mastocytoma P815. VIII. Detection of stable transfectants expressing a tum- antigen with a cytolytic T cell stimulation assay. Immunogenetics 1987; 26: 178-187. (PMID: 3114137) Download PDF

Lurquin C, Van Pel A, Mariamé B, De Plaen E, Szikora J-P, Janssens C, Reddehase M, Lejeune J, Boon T. Structure of the gene coding for tum- transplantation antigen P91A. A peptide encoded by the mutated exon is recognized with Ld by cytolytic T cells. Cell 1989 Jul 28; 58: 293-303. (PMID: 2568889)
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1989
Major Discovery
DEMONSTRATION OF THE PRESENCE OF DISTINCT ANTIGENS RECOGNIZED BY CTL ON HUMAN MELANOMA
Details
November 09, 1989
Major Discovery
DEMONSTRATION OF THE PRESENCE OF DISTINCT ANTIGENS RECOGNIZED BY CTL ON HUMAN MELANOMA
Studying antigen-loss variants obtained in vitro with specific CTL clones, Thomas Wölfel, Alex Knuth, Gerard Degiovanni, Benoit Van den Eynde, Philippe Hainaut, and Thierry Boon demonstrate the presence of distinct antigens recognized by CTL on human melanoma. These antigen-loss variants will prove instrumental for the subsequent cloning of human tumor antigens.
 

Degiovanni G, Lahaye T, Hérin M, Hainaut P, Boon T. Antigenic heterogeneity of a human melanoma tumor detected by autologous CTL clones. Eur J Immunol 1988 May; 18: 671-676. (PMID: 2967757)

Knuth A, Wölfel T, Klehmann E, Boon T, Meyer zum Büschenfelde K-H. Cytolytic T-cell clones against an autologous human melanoma: specificity study and definition of three antigens by immunoselection. Proc Natl Acad Sci U S A 1989 Apr; 86: 2804-2808. (PMID: 2784858) Download PDF

Van den Eynde B, Hainaut P, Hérin M, Knuth A, Lemoine C, Weynants P, van der Bruggen P, Fauchet R, Boon T. Presence on a human melanoma of multiple antigens recognized by autologous CTL. Int J Cancer 1989 Oct 15; 44: 634-640. (PMID: 2529220)
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1989
Major Discovery
FIRST USE OF THE T-BODY APPROACH
Details
November 09, 1989
Major Discovery
FIRST USE OF THE T-BODY APPROACH

1989-Zelig-Eshhar.jpgZelig Eshhar and colleagues first use the T-body approach, employing chimeric receptors composed of an antibody recognition unit linked to T cell activation domains, to redirect T cells to recognize and attack tumor cells.
 



Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity (chimeric genes/antibody variable region). Proc Natl Acad Sci U S A 1989 Dec; 86: 10024-10028. (PMID: 2513569) Download PDF

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1989
Major Discovery
IDENTIFICATION AND CLONING OF THE RAG-1 AND RAG-2
Details
November 09, 1989
Major Discovery
IDENTIFICATION AND CLONING OF THE RAG-1 AND RAG-2
David Baltimore and David Schatz identify and clone the RAG-1 and RAG-2 genes, whose protein products are essential for V(D)J joining.

Schatz DG, Oettinger MA, Baltimore D. The V(D)J recombination activating gene, RAF-1 Cell 1989 Dec 22; 59: 1035. (PMID: 2598259)

Oettinger MA, Schatz DG, Gorka C, Baltimore D. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science 1990 Jun 22; 248: 1517. (PMID: 2360047)
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1989
Major Discovery
INTERLEUKIN-12 (IL-12) IDENTIFIED
Details
November 09, 1989
Major Discovery
INTERLEUKIN-12 (IL-12) IDENTIFIED

1989-Giorgio-Trinchieri.jpgGiorgio Trinchieri and his team at the Wistar Institute identify interleukin-12 (IL-12), a cytokine that helps regulate the body’s resistance to infections and cancer.



Kobayashi M, Fitz L, Ryan M, Hewick RM, Clark SC, Chan S, Loudon R, Sherman F, Perussia B, Trinchieri G. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med 1989 Sep 1; 170: 827-845. (PMID: 2504877) Download PDF

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1989
Treatment Approved
CARBOPLATIN APPROVED BY FDA
Details
November 09, 1989
Treatment Approved
CARBOPLATIN APPROVED BY FDA

1989-Carboplatin.jpgCarboplatin is approved by the FDA to treat cancer.

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1989
Awards & Honors
NOBEL PRIZE FOR THE FIRST PROTO-ONCOGENE DISCOVERERS
Details
November 09, 1989
Awards & Honors
NOBEL PRIZE FOR THE FIRST PROTO-ONCOGENE DISCOVERERS
Nobel Prize is awarded to Harold Varmus and Michael Bishop for discovering the first proto-oncogene (Src).
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1989
Major Discovery
PEPTIDE PROVED TO BE AN ESSENTIAL SUBUNIT OF CLASS I MHC PRODUCT
Details
November 09, 1989
Major Discovery
PEPTIDE PROVED TO BE AN ESSENTIAL SUBUNIT OF CLASS I MHC PRODUCT
Alain Townsend and Klas Kärre demonstrate that peptide is an essential subunit of class I MHC product.


Townsend A, Ohlen C, Bastin J, Ljunggren H-G, Foster L, Kärre K. Association of class I major histocompatibility heavy and light chains induced by viral peptides. Nature 1989 Aug 10; 340: 443–448. (PMID: 2666863) (Pillars) Download PDF
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1989
Field Milestone
HYPOTHESIS INVOLVING MICROBIAL AGENTS INTRODUCED
Details
November 09, 1989
Field Milestone
HYPOTHESIS INVOLVING MICROBIAL AGENTS INTRODUCED

1989-Charles-Janeway.jpgCharles Janeway introduces the hypothesis that “components of the innate [immune] system, especially antigen-presenting cells such as DCs, required the microbial stimuli contained in [adjuvants] to become activated and acquire the capacity to induce productive responses from antigen-specific lymphocytes. Without such activation by recognition of infection, Janeway suggested that the adaptive immune system ignored or even became tolerant to the antigens presented by the ‘quiescent’ DC. He specifically proposed that evolutionarily conserved features of infectious organisms (pathogen-associated molecular patterns or PAMPs) were detected by the immune system through a set of specialized receptors (which he termed pattern-recognition receptors or PRRs), an especially prescient aspect of this hypothesis. Matzinger’s competing ‘Danger Model’ argued against Janeway’s focus on microbial agents.”


Janeway CA, Jr. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 1989; 1: 1-13. (PMID: 2700931)

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1989
Major Discovery
MUTATIONS IN THE P53 GENE FOUND TO PLAY A ROLE IN HUMAN CANCER DEVELOPMENT
Details
November 09, 1989
Major Discovery
MUTATIONS IN THE P53 GENE FOUND TO PLAY A ROLE IN HUMAN CANCER DEVELOPMENT

1989-Bert-Vogelstein.jpgBert Vogelstein and colleagues find that mutations in the p53 gene play a role in the development of many common human cancers.
 



Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins FS, Weslon A, Modali R, Harris CC, Vogelstein B. Mutations in the p53 gene occur in diverse human tumour types. Nature 1989 Dec 7; 342: 705-708. (PMID: 2531845)

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1989
CRI Milestone
CRI LAUNCHED RUSSIA PROGRAM
Details
November 09, 1989
CRI Milestone
CRI LAUNCHED RUSSIA PROGRAM
With the emergence of Glasnost and with the assistance of the Samuel Freeman Charitable Trust, CRI begins the Russia Program to foster collaboration between U.S. and Russian scientists.
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1989
Awards & Honors
CRI'S COLEY AWARD FOR DISCOVERIES ON T CELL ANTAGONISM AND MHC ANTIGEN PROCESSING
Details
November 09, 1989
Awards & Honors
CRI'S COLEY AWARD FOR DISCOVERIES ON T CELL ANTAGONISM AND MHC ANTIGEN PROCESSING
CRI presents the Coley Award to Howard Grey, for the discovery of T cell antagonism, and to Alain Townsend and Emil Unanue for fundamental discoveries related to MHC antigen processing.
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1989
Major Discovery
HUMAN HOMOLOGUE OF THE MOUSE TUMOR REJECTION ANTIGEN IDENTIFIED
Details
November 09, 1989
Major Discovery
HUMAN HOMOLOGUE OF THE MOUSE TUMOR REJECTION ANTIGEN IDENTIFIED

1984-Lloyd-J-Old.jpgPramod Srivastava and Lloyd J. Old identify the human homologue of the mouse tumor rejection antigen gp96.



Srivastava PK, Old LJ. Identification of the human homologue of the murine tumor rejection antigen gp96. Cancer Res 1989 Mar 15; 49: 1341-1343. (PMID: 2924290) Download PDF

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1988
Major Discovery
BIOCHEMICAL INITIATORS OF T CELL ACTIVATION DISCOVERED
Details
November 09, 1988
Major Discovery
BIOCHEMICAL INITIATORS OF T CELL ACTIVATION DISCOVERED
Christopher E. Rudd and Stuart F. Schlossman discover the biochemical initiators of T cell activation, CD4- and CD8-p56lck complexes.
 

Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF. The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (Pp58) from human T lymphocytes. Proc Natl Acad Sci U S A 1988 Jul; 85: 5190-5194. (PMID: 2455897) (Pillars) Download PDF
 
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1988
Major Discovery
CLONING OF CTLA-4
Details
November 09, 1988
Major Discovery
CLONING OF CTLA-4
The gene for the human cytotoxic T lymphocyte-associated antigen (CTLA-4) is cloned.
 

Dariavach P, Mattei MG, Golstein P, Lefranc MP. Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains. Eur J Immunol 1988 Dec; 18: 1901-1905. (PMID: 3220103)
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1988
Major Discovery
THE FIRST ISOLATION OF HEMATOPOIETIC STEM CELLS IN MICE
Details
November 09, 1988
Major Discovery
THE FIRST ISOLATION OF HEMATOPOIETIC STEM CELLS IN MICE

1988-Irving-L-Weissman.jpgIrving L. Weissman and colleagues are the first to isolate hematopoietic stem cells in mice.
 



Spangrude GJ, Heimfeld S, Weissman IL. Purification and characterization of mouse hematopoietic stem cells. Science 1988 Jul 1; 241: 58-62. (PMID: 2898810)

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1988
Major Discovery
NEW DISCOVERIES ON CELL SURVIVAL AND IMPAIRED CELL DEATH
Details
November 09, 1988
Major Discovery
NEW DISCOVERIES ON CELL SURVIVAL AND IMPAIRED CELL DEATH
David Vaux, Suzanne Cory, and Jerry Adams provide evidence that cell survival is regulated independently of cell proliferation, and that impaired cell death, similar to enhanced proliferation, is a key step in tumor development.
 

Vaux DL, Cory S, Adams JM. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 1988 Sep 29; 335: 440-442. (PMID: 3262202)
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1988
CRI Milestone
CRI'S WORKSHOP ON T CELL PATTERN RECOGNITION INITIATED
Details
November 09, 1988
CRI Milestone
CRI'S WORKSHOP ON T CELL PATTERN RECOGNITION INITIATED
September 26-27: CRI Workshop: T-Cell Pattern Recognition, New York, NY
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1988
CRI Milestone
CRI ISSUES NEW PUBLICATION OF INVESTING IN CANCER IMMUNOLOGY
Details
November 09, 1988
CRI Milestone
CRI ISSUES NEW PUBLICATION OF INVESTING IN CANCER IMMUNOLOGY
CRI issues Investing in Cancer Immunology: New Hope for Cancer Control and Cancer and the Immune System: The Vital Connection.
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1988
Major Discovery
FIRST EVIDENCE OF A PHYSICAL LINK BETWEEN ONCOPROTEINS AND TUMOR SUPPRESSORS PROVIDED
Details
November 09, 1988
Major Discovery
FIRST EVIDENCE OF A PHYSICAL LINK BETWEEN ONCOPROTEINS AND TUMOR SUPPRESSORS PROVIDED
Researchers show that viral oncoproteins E1A of adenovirus,[i] large tumor antigen of SV40,[ii] and E7 of papillomavirus[iii] bind to the retinoblastoma tumor suppressor protein, providing the first evidence of a physical link between oncoproteins and tumor suppressors.


[i] Whyte P, Buchkovich KJ, Horowitz JM, Friend SH, Raybuck M, Weinberg RA, Harlow E. Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature 1988 Jul 14; 334: 124-129. (PMID: 2968522)

[ii] DeCaprio JA, Ludlow JW, Figge J, Shew JY, Huang CM, Lee WH, Marsilio E, Paucha E, Livingston DM. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 1988 Jul 15; 54: 275-283. (PMID: 2839300)

[iii] Dyson N, Howley PM, Münger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 1989 Feb 17; 243: 934-937. (PMID: 2537532)

 
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1987
Major Discovery
DISCOVERY OF HOW HLA PROTEIN AND ANTIGEN ARE PRESENTED SIMULTANEOUSLY TO T CELLS
Details
November 09, 1987
Major Discovery
DISCOVERY OF HOW HLA PROTEIN AND ANTIGEN ARE PRESENTED SIMULTANEOUSLY TO T CELLS
Pamela Bjorkman, Jack Strominger, and Don Wiley solve the 3-D crystal structure of HLA-A2 (an MHC class I protein) complexed with peptide, revealing how HLA protein and antigen are presented simultaneously to T cells.
 

Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC. Structure of the human class I histocompatibility antigen, HLA-A2. Nature 1987 Oct 8-14; 329: 506-512. (PMID: 3309677) Download PDF

Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 1987 Oct 8-14; 329: 512-518. (PMID: 2443855)

 
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1987
Awards & Honors
NOBEL PRIZE FOR ANTIBODY DIVERSITY
Details
November 09, 1987
Awards & Honors
NOBEL PRIZE FOR ANTIBODY DIVERSITY

1987-Susumu-Tonegawa.jpgSusumu Tonegawa receives the Nobel Prize in Physiology or Medicine for his discovery of the genetic principle for the generation of antibody diversity.

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1987
Major Discovery
NEGATIVE SELECTION IN THE THYMUS CONFIRMED
Details
November 09, 1987
Major Discovery
NEGATIVE SELECTION IN THE THYMUS CONFIRMED
John Kappler and Philippa Marrack confirm negative selection in the thymus.

Kappler JW, Roehm N, Marrack P. T cell tolerance by clonal elimination in the thymus. Cell 1987 Apr 24; 49: 273-280. (PMID: 3494522)
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1987
Major Discovery
NEW AVENUE OPENED FOR THE STUDY OF SOMATIC HYPERMUTATION
Details
November 09, 1987
Major Discovery
NEW AVENUE OPENED FOR THE STUDY OF SOMATIC HYPERMUTATION
Rebecca O’Brien and Ursula Storb are the first to show that Ig transgenes can be somatically hypermutated, opening a new avenue for the study of somatic hypermutation.

O’Brien R, Brinster R, Storb U. Somatic hypermutation of an immunoglobulin transgene in k transgenic mice. Nature 1987 Mar 26-Apr 1; 326: 405-409. (PMID: 3104790)
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1987
Major Discovery
CLONING OF TUMOR SUPPRESSOR GENE
Details
November 09, 1987
Major Discovery
CLONING OF TUMOR SUPPRESSOR GENE
Stephen Friend, Robert Weinberg, and colleagues report the cloning of the human retinoblastoma (RB) gene, which is identified as a tumor suppressor gene.
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1987
Major Discovery
PROGRESS ON THE TREATMENT OF ADVANCED CANCER
Details
November 09, 1987
Major Discovery
PROGRESS ON THE TREATMENT OF ADVANCED CANCER
Steven Rosenberg reports on a trial of 157 patients with advanced cancer treated with LAK cells and IL-2 or high dose IL-2 alone, achieving 9 complete regressions, with an additional 20 patients undergoing a reduction in their cancer of 50 percent or more.

Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp C, Simpson CG, White DE. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 1987 Apr 9; 316: 889-897. (PMID: 3493432)
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1987
Major Discovery
FIRST PATIENT WITH AUTOLOGOUS TUMOR-INFILTRATING LYMPHOCYTES TREATED
Details
November 09, 1987
Major Discovery
FIRST PATIENT WITH AUTOLOGOUS TUMOR-INFILTRATING LYMPHOCYTES TREATED
Steven A. Rosenberg and colleagues treat the first patient with autologous tumor-infiltrating lymphocytes cultured with IL-2, achieving regressions in 9 of 15 melanoma patients.

Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA, Simpson C, Carter C, Bock S, Schwartzentruber D, Wei JP, White DE. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 1988 Dec 22; 319: 1676-1680. (PMID: 3264384)
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1987
Major Discovery
FIRST DESCRIPTION OF AN ANTIGEN-SPECIFIC FORM OF T CELL ANERGY PROVIDED
Details
November 09, 1987
Major Discovery
FIRST DESCRIPTION OF AN ANTIGEN-SPECIFIC FORM OF T CELL ANERGY PROVIDED
Marc Jenkins and Ron Schwartz provide the first description of an antigen-specific form of T cell anergy.

Jenkins MK, Schwartz RH. Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med 1987 Feb 1; 165: 302-319. (PMID: 3029267) (Pillars) Download PDF
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1987
Major Discovery
THE FIRST STABLE HUMAN ANTI-TUMOR CTL CLONES ISOLATED
Details
November 09, 1987
Major Discovery
THE FIRST STABLE HUMAN ANTI-TUMOR CTL CLONES ISOLATED
Michel Hérin, Aline Van Pel, Alex Knuth, and Thierry Boon isolate the first stable human anti-tumor cytotoxic T lymphocyte (CTL) clones, and maintain them in long-term culture. The clones were isolated from the blood of a melanoma patient with long-term remission following vaccination with irradiated mutagenized autologous tumor cells.

Hérin M, Lemoine C, Weynants P, Vessière F, Van Pel A, Knuth A, Devos R, Boon T. Production of stable cytolytic T-cell clones directed against autologous human melanoma. Int J Cancer 1987 Mar 15; 39: 390-396. (PMID: 3493226)
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1987
Major Discovery
CTLA-4 IDENTIFIED
Details
November 09, 1987
Major Discovery
CTLA-4 IDENTIFIED

1994-CTLA-4.pngThe cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is identified.



Brunet JF, Denizot F, Luciani MF, Roux-Dosseto M, Suzan M, Mattei MG, Golstein P. A new member of the immunoglobulin superfamily--CTLA-4. Nature 1987 Jul 16-22; 328: 267-270. (PMID: 3496540)

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1987
Major Discovery
FIRST DIRECT EVIDENCE PROVIDED FOR THE INTERACTION BETWEEN CD4 AND MHC CLASS II
Details
November 09, 1987
Major Discovery
FIRST DIRECT EVIDENCE PROVIDED FOR THE INTERACTION BETWEEN CD4 AND MHC CLASS II

Carolyn Doyle and Jack Strominger provide the first direct evidence that CD4 bound to MHC class II and that this interaction could mediate cell adhesion.



Doyle C, Strominger JL. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature 1987 Nov 19-25; 330: 256-259. (PMID: 2823150) Download PDF
 

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1987
Major Discovery
GAMMA-DELTA T CELLS ESTABLISHED AS AN INDEPENDENT THIRD ARM OF THE ADAPTIVE IMMUNE SYSTEM
Details
November 09, 1987
Major Discovery
GAMMA-DELTA T CELLS ESTABLISHED AS AN INDEPENDENT THIRD ARM OF THE ADAPTIVE IMMUNE SYSTEM
Several groups provide immunological and biochemical evidence demonstrating that the gamma-delta molecule is a second T cell receptor consisting of two variable protein chains, gamma and delta, establishing gamma-delta T cells as an independent third arm of the adaptive immune system, together with B cells and alpha-beta T cells.
 

Hata S, Brenner MB, Krangel MS. Identification of putative human T cell receptor delta complementary DNA clones. Science 1987 Oct 30; 238: 678-682. (PMID: 3499667)

Band H, Hochstenbach F, McLean J, Hata S, Krangel MS, Brenner MB. Immunochemical proof that a novel rearranging gene encodes the T cell receptor delta subunit. Science 1987 Oct 30; 238: 682-684. (PMID: 3672118)

Loh EY, Lanier LL, Turck CW, Littman DR, Davis MM, Chien YH, Weiss A. Identification and sequence of a fourth human T cell antigen receptor chain. Nature 1987 Dec 10-16; 330: 569-572; (PMID: 2825032)

Born W, Miles C, White J, O’Brien R, Freed JH, Marrack P, Kappler J, Kubo RT. Peptide sequences of T-cell receptor delta and gamma chains are identical to predicted X and gamma proteins. Nature 1987 Dec 10-16; 330: 572-574. (PMID: 3500416)

Bonyhadi M, Weiss A, Tucker PW, Tigelaar RE, Allison JP. Delta is the Cx-gene product in the gamma/delta antigen receptor of dendritic epidermal cells. Nature 1987 Dec 10-16; 330: 574-576. (PMID: 3500417)
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1987
Major Discovery
CLONING OF INTERLEUKIN 5
Details
November 09, 1987
Major Discovery
CLONING OF INTERLEUKIN 5
Ian G. Young and colleagues clone human eosinophil differentiation factor (interleukin 5).

Campbell HD, Tucker WQ, Hort Y, Martinson ME, Mayo G, Clutterbuck EJ, Sanderson CJ, Young IG. Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5). Proc Natl Acad Sci U S A 1987 Oct; 84: 6629-6633. (PMID: 3498940) Download PDF
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1987
Major Discovery
CD8 CORECEPTOR PROVED TO BE ACTIVELY INVOLVED IN ANTIGEN RECOGNITION BY KILLER T CELLS
Details
November 09, 1987
Major Discovery
CD8 CORECEPTOR PROVED TO BE ACTIVELY INVOLVED IN ANTIGEN RECOGNITION BY KILLER T CELLS
Harald von Boehmer and colleauges, including Rose Zamoyska and Michael Steinmetz, show that the CD8 coreceptor is actively involved in antigen recognition by killer T cells.

Dembić Z, Haas W, Zamoyska R, Parnes J, Steinmetz M, von Boehmer H. Transfection of the CD8 gene enhances T-cell recognition. Nature 1987 Apr 2-8; 326: 510-511. (PMID: 3031507)
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1987
CRI Milestone
CRI DEVELOPED WORKSHOPS TO EXPLORE CUTTING-EDGE OF CANCER IMMUNOLOGY
Details
November 09, 1987
CRI Milestone
CRI DEVELOPED WORKSHOPS TO EXPLORE CUTTING-EDGE OF CANCER IMMUNOLOGY
CRI commences workshops exploring topics at the cutting-edge of cancer immunology. The first workshop focuses on Immune Responses to Human Melanoma.
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1987
Awards & Honors
THIERRY BOON AND ROLF M. ZINKERNAGEL WON CRI'S COLEY AWARD
Details
November 09, 1987
Awards & Honors
THIERRY BOON AND ROLF M. ZINKERNAGEL WON CRI'S COLEY AWARD
CRI presents the Coley Award to Thierry Boon, for the isolation of genes responsible for mutation-induced production of cancer antigens by T cells, and to Rolf M. Zinkernagel, for landmark discoveries about MHC restriction of T cell recognition.
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1987
Major Discovery
CD4 AND CD8 CELLS MEDIATE MHC CLASS I AND CLASS II SKIN GRAFT REJECTION
Details
November 09, 1987
Major Discovery
CD4 AND CD8 CELLS MEDIATE MHC CLASS I AND CLASS II SKIN GRAFT REJECTION
Eiichi Nakayama and colleagues report in vivo rejection of MHC class I- and class II-disperate skin graft by CD8 and CD4, respectively.

Ichikawa T, Nakayama E, Uenaka A, Monden M, Mori T. Effector cells in allelic H-2 class I-incompatible skin graft rejection. J Exp Med 1987 Oct 1; 166: 982-990. (PMID: 3309129) Download PDF

Kawai M, Obata Y, Hamasima N, Takahashi T, Uenaka A, Monden M, Mori T, Shiku H, Nakayama E. Differential involvement of CD4+ cells in mediating skin graft rejection against different amounts of transgenic H-2K(b) antigen. J Exp Med 1991 Jan 1; 173: 261-264. (PMID: 1670639) Download PDF
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1986
Major Discovery
FC-GAMMA RECEPTORS CLONED
Details
November 09, 1986
Major Discovery
FC-GAMMA RECEPTORS CLONED
The laboratories of Ira Mellman and of Jeffrey Ravetch (including 1984-1986 CRI Fellow Jarema Kochan in the Ravetch laboratory) clone the first mouse, then human, Fc-gamma receptors, providing the first insight into this important class of signaling receptors on various immune effector and regulatory cells.

Lewis VA, Koch T, Plutner H, Mellman I. A complementary DNA clone for macrophage-lymphocyte Fc receptor. Nature 1985 Nov 27-Dec 3; 324: 372-375. (PMID: 3024012) Ravetch JV, Luster Ad, Weinshank R, Kochan J, Pavlovec A, Portnoy DA, Hulmes J, Pan YC, Unkeless JC. Structural heterogeneity and functional domains of murine immunoglobulin G Fc receptors. Science 1986 Nov 7; 234: 718-725. (PMID: 2946078)
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1986
Tools & Technologies
FIRST HUMANIZED ANTIBODIES CREATED
Details
November 09, 1986
Tools & Technologies
FIRST HUMANIZED ANTIBODIES CREATED
Greg Winter produces the first humanized antibody by replacing the complementarity regions in a human antibody with those of a mouse. Winter also developed techniques to fully humanize antibodies for therapeutic use.

Jones PT, Dear PH, Foote J, Neuberger MS, Winter G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 1986 May 29-Jun 4; 321: 522-525. (PMID: 3713831)
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1986
Treatment Approved
FIRST MONOCLONAL ANTIBODY APPROVED FOR PREVENTION OF TRANSPLANTATION REJECTION
Details
November 09, 1986
Treatment Approved
FIRST MONOCLONAL ANTIBODY APPROVED FOR PREVENTION OF TRANSPLANTATION REJECTION
The first monoclonal antibody, muromonab-CD3 (Orthoclone OKT3), is approved by the FDA for the prevention of transplantation rejection. Orthoclone OKT3 was developed by Patrick Kung at Ortho Diagnostic Systems and Stuart Schlossman at Dana-Farber Cancer Institute.
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1986
CRI Milestone
CRI ESTABLISHED INVESTIGATOR AWARD PROGRAM
Details
November 09, 1986
CRI Milestone
CRI ESTABLISHED INVESTIGATOR AWARD PROGRAM
Cancer Research Institute inaugurates its Investigator Award Program for junior faculty members working in immunology and tumor immunology. The first recipients, awarded in January 1987, include Avraham Ben-nun, Alan N. Houghton, David H. Raulet, Haruo Saito, and John Ding-E Young.
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1986
CRI Milestone
CRI WELCOMES ITS FIRST FEMALE MEMBER IN SCIENTIFIC ADVISORY COUNCIL
Details
November 09, 1986
CRI Milestone
CRI WELCOMES ITS FIRST FEMALE MEMBER IN SCIENTIFIC ADVISORY COUNCIL

Philippa-Marrack.jpgPhilippa Marrack, of the National Jewish Center for Immunology and Respiratory Medicine, Denver, CO, becomes the first woman to join the Cancer Research Institute Scientific Advisory Council.

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1986
Major Discovery
PEPTIDE LENGTH IDENTIFIED AS A FACTOR CONTRIBUTING TO RECOGNITION OF ANTIGEN BY CD8+ T LYMPHOCYTES
Details
November 09, 1986
Major Discovery
PEPTIDE LENGTH IDENTIFIED AS A FACTOR CONTRIBUTING TO RECOGNITION OF ANTIGEN BY CD8+ T LYMPHOCYTES

1986-Andrew-J-McMichael.jpgAlain R. Townsend and Andrew J. McMichael demonstrate that peptide length is a factor contributing to recognition of antigen by CD8+ T lymphocytes, specifically that MHC class I molecules bind short peptides.
 



Townsend ARM, Rothbard J, Gotch FM, Bahadur G, Wraith D, McMichael AJ. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 1986 Mar 28; 44: 959–968. (PMID: 2420472)

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1986
Major Discovery
TH1/TH2 MODEL OF T HELPER CELL FUNCTION PROPOSED
Details
November 09, 1986
Major Discovery
TH1/TH2 MODEL OF T HELPER CELL FUNCTION PROPOSED

1986-Timothy-Mosmann.jpgTimothy Mosmann and Robert Coffman propose the Th1/Th2 model of T helper cell function. Th1 cells produce interferon-gamma, which plays an important role in anti-tumor immunity and in defending against intracellular pathogens, whereas Th2 cells generate IL-4, IL-5, and IL-13, which protect against parasitic infections and help mediate antibody responses.
 



Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986 Apr 1; 136: 2348-2357. (PMID: 2419430) Download PDF

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1986
Major Discovery
CLONING OF THE GENE ENCODING FOR IL-4
Details
November 09, 1986
Major Discovery
CLONING OF THE GENE ENCODING FOR IL-4

1986-Frank-Lee.jpgTwo groups, led by Frank Lee at DNAX Research Institute[i] and by Tasuku Honjo at Kyoto University,[ii] clone the gene encoding for IL-4.




[i] Lee F, Yokota T, Otsuka T, Meyerson P, Meyerson P, Villaret D, Coffman D, Mosmann T, Rennick D, Roehm N, Smith C, Zlotnick A, Arai K-I. Isolation and characterization of a mouse interleukin cDNA clone that expresses B-cell stimulatory factor activities and T-cell and mast cell-stimulating activities. Proc Natl Acad Sci U S A 1986 Apr; 83: 2061-2065. (PMID: 3083412) Download PDF

[ii] Noma Y, Sideras T, Naito T, Bergstedt-Lindqvist S, Azuma C, Severinson E, Takabe T, Kinashi K, Matsuda F, Yaoita Y, Honjo T. Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter. Nature 1986 Feb 20-26; 319: 640-646. (PMID: 3005865)

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1986
Major Discovery
T4 (CD4) IDENTIFIED AS THE MOLECULE THAT ENABLES HIV TO ENTER IMMUNE SYSTEM CELLS
Details
November 09, 1986
Major Discovery
T4 (CD4) IDENTIFIED AS THE MOLECULE THAT ENABLES HIV TO ENTER IMMUNE SYSTEM CELLS

1985-Richard-A-Axel-1.jpgRichard Axel and colleagues, including Leonard Chess and Dan Littman, identify T4 (CD4) as the molecule that enables HIV to enter immune system cells.


 


McDougal JS, Maddon PJ, Dalgliesh AG, Clapham PR, Littman DR, Godfrey M, Maddon DE, Chess L, Weiss RA, Axel R. 1986. The T4 glycoprotein is a cell-surface receptor for the AIDS virus. Cold Spring Harbor Symp Quant Biol 1986; 51 (pt. 2): 703-711. (PMID: 3495395)

 

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1986
Major Discovery
NEW DISCOVERY ON IMMUNORECEPTORS
Details
November 09, 1986
Major Discovery
NEW DISCOVERY ON IMMUNORECEPTORS

1986-Larry-Samelson.jpgLarry Samelson provides the first demonstration that the TCR is coupled to tyrosine kinase pathways, now known to be true for all immunoreceptors.



Samelson LE, Patel MD, Weissman AM, Harford JB, Klausner RD. Antigen activation of murine T cells induces tyrosine phosphorylation of a polypeptide associated with the T cell antigen receptor. Cell 1986 Sep 26; 46: 1083-1090. (PMID: 2428504)

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1986
Major Discovery
DISCOVERY ON NATURAL KILLER CELLS
Details
November 09, 1986
Major Discovery
DISCOVERY ON NATURAL KILLER CELLS

1986-Klas-Karre.jpgKlas Kärre, with Rolf Kiessling, reports on experiments suggesting that natural killer cells are inhibited, not activated, by interacting with MHC class I.
 



Kärre K, Ljunggren HG, Piontek G, Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 1986 Feb 20-26; 391: 675-678. (PMID: 3951539) Download PDF
 

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1986
Major Discovery
FINDINGS OF HIGH-DOSE INTERLEUKIN-2 ON ANTI-TUMOR RESPONSE
Details
November 09, 1986
Major Discovery
FINDINGS OF HIGH-DOSE INTERLEUKIN-2 ON ANTI-TUMOR RESPONSE

1986-Steven-Rosenberg-1.jpgSteven Rosenberg and colleagues report anti-tumor responses in 3 of 10 patients treated with high-dose interleukin-2 alone.



Lotze MT, Chang AE, Seipp CA, Simpson C, Vetto JT, Rosenberg SA. High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer. Responses, treatment-related morbidity, and histologic findings. JAMA 1986 Dec 12; 256: 3117-3124. (PMID: 3491225)
 

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1986
Major Discovery
PDF LINK BROKEN TRANSCRIPTION FACTOR NUCLEAR FACTOR KAPPA BETA IDENTIFIED
Details
November 09, 1986
Major Discovery
PDF LINK BROKEN TRANSCRIPTION FACTOR NUCLEAR FACTOR KAPPA BETA IDENTIFIED
Ranjan Sen and David Baltimore identify the transcription factor nuclear factor kappa beta (NFκB).
 

Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 1986 Aug 29; 46: 705-715. (PMID: 3091258) Download PDF
 
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1986
Major Discovery
ADHESION MOLECULES IDENTIFIED
Details
November 09, 1986
Major Discovery
ADHESION MOLECULES IDENTIFIED

Timothy Springer, with colleagues Michael L. Dustin and Charles A. Dinarello, identifies and characterizes adhesion molecules, a class of cell surface proteins that function in the interactions of immune cells with other cells, including antigen-specific recognition and cell trafficking: integrin LFA-1 involved in cytoskeleton and signaling, and intracellular adhesion molecules (ICAMs), which are binding partners (ligands) for LFA-1 and are increased in inflammatory and autoimmune disease.
 



Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 1986 Jul 1; 137: 245–254. (PMID: 3086451) Download PDF

Rothlein R, Dustin ML, Marlin SD, Springer TA. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol 1986 Aug 15; 137: 1270–1274. (PMID: 3525675) Download PDF

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1986
Tools & Technologies
THE FIRST ANTI-MURINE MONOCLONAL ANTI-CD3 ANTIBODY DEVELOPED
Details
November 09, 1986
Tools & Technologies
THE FIRST ANTI-MURINE MONOCLONAL ANTI-CD3 ANTIBODY DEVELOPED
Jeffrey Bluestone, Larry Samelson, and colleagues develop the first anti-murine monoclonal anti-CD3 antibody.[i] The development of the antibody and a better understanding of mechanism of action and side effects led to development of first humanized anti-CD3 with Fc mutation for the treatment of autoimmune disease.[ii]
 

[i] Leo O, Foo M, Sachs DH, Samelson LE, Bluestone JA. Identification of a monoclonal antibody specific for murine T3. Proc Natl Acad Sci U S A 1987 Mar; 84: 1374-1378. (PMID: 2950524) Download PDF

[ii] Alegre M-L, Collins AM, Pulito VL, Brosius RA, Olson WC, Zivin RA, Knowles R, Thistlethwaite JR, Jolliffe LK, Bluestone JA. Effect of a single amino acid mutation on the activating and immunosuppressive properties of a “humanized” OKT3 monoclonal antibody in vitro. J Immunol 1992 Jun 1; 148: 3461-3468. (PMID: 1534096) Herold KC, Bluestone JA, Montag AG, Parihar A, Wiegner A, Gress RE, Hirsch R. Prevention of autoimmune diabetes with nonactivating anti-CD3 monoclonal antibody. Diabetes 1992 Mar; 41: 385-391. (PMID: 1532369)
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1986
Major Discovery
GAMMA-DELTA T LYMPHOCYTES DISCOVERED
Details
November 09, 1986
Major Discovery
GAMMA-DELTA T LYMPHOCYTES DISCOVERED
In two papers published in Nature, Michael B. Brenner, with Jack Strominger, Jonathan Seidman, and others, and with Ilan Bank, Ronald DePinho, Judy Cassimeris, Frederick Alt, and Leonard Chess, reports the discovery of gamma-delta T lymphocytes.

Brenner MB, McLean J, Dialynas DP, Strominger JL, Smith JA, Owen FL, Seidman JC, Ip S, Rocon F, Krangel MS. Identification of a putative second T cell receptor. Nature 1986 Jul 10-16; 322: 145-149. (PMID: 375522)

Bank I, DePinho RA, Brenner MB, Cassimeris J, Alt FW, Chess L. A functional T3 molecule associated with a novel heterodimer on the surface of immacture human thymocytes. Nature 1986 Jul 10-16; 322: 179-181. (PMID: 3487737)

 
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1985
Major Discovery
NEW TRANSGENIC MOUSE MODEL DEVELOPED TO STUDY CANCER
Details
November 09, 1985
Major Discovery
NEW TRANSGENIC MOUSE MODEL DEVELOPED TO STUDY CANCER
Lynn Corcoran and colleagues Jerry Adams, Suzanne Cory, with Ralph Brinster and Richard Palmiter, develop the Eµ-myc mouse, a lymphoma-prone transgenic mouse used in many subsequent studies, including the assessment of oncogene cooperation and the efficacy of novel anti-cell survival drugs for lymphoma therapy.

Adams JM, Harris AW, Pinkert CA, Corcoran LM, Alexander WS, Cory S, Palmiter RD, Brinster RL. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 1985 Dec 12-18; 318: 533-538. (PMID: 3906410) Based on this original finding: Corcoran LM, Cory S, Adams JM. Transposition of the immunoglobulin heavy chain enhancer to the myc oncogene in a murine plasmacytoma. Cell 1985 Jan; 40: 71-79. (PMID: 2981633)
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1985
Major Discovery
LAK CELLS + IL-2 INDUCE REGRESSION OF METASTASES IN MELANOMA AND RENAL CANCER
Details
November 09, 1985
Major Discovery
LAK CELLS + IL-2 INDUCE REGRESSION OF METASTASES IN MELANOMA AND RENAL CANCER
Steven A. Rosenberg and colleagues report that treatment with high doses of IL-2 and LAK cells caused regression of metastases in patients with melanoma and renal cell cancer, representing the first to describe the mediation of cancer regression in humans by an IL-2-based immunotherapy.

Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT, Seipp CA, Simpson C, Reichert CM. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 1985 Dec 5; 313: 1485-1492. (PMID: 3903508)
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1985
Tools & Technologies
POLYMERASE CHAIN REACTION (PCR) DEVELOPED
Details
November 09, 1985
Tools & Technologies
POLYMERASE CHAIN REACTION (PCR) DEVELOPED
Kary Banks Mullis, Henry A. Erlich, and colleagues conceive that a fragment of DNA could be forced to replicate itself many times in a test tube, the origin of polymerase chain reaction (PCR).

Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985 Dec 20; 230: 1350-1354. (PMID: 2999980) Mullis K, Faloona F, Scharf S, Saiki R, Horn G, Erlich H. Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. Cold Spring Harb Symp Quant Biol 1986; 51 Pt 1: 263-273. (PMID: 3472723)
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1985
Major Discovery
ORGANIZATION OF IMMUNOGLOBULIN GENES REPORTED
Details
November 09, 1985
Major Discovery
ORGANIZATION OF IMMUNOGLOBULIN GENES REPORTED

1985-Susumu-Tonegawa.jpgSusumu Tonegawa, Leroy Hood, and colleagues report on the organization of immunoglobulin genes, demonstrating how so many antibody patterns can be produced by such a limited number of genes. These ideas were also very important in understanding the structure and formation of the T cell receptor.

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1985
Major Discovery
IN VIVO DEPLETION OF CD8 T CELLS REPORTED
Details
November 09, 1985
Major Discovery
IN VIVO DEPLETION OF CD8 T CELLS REPORTED

1985-Eiichi-Nakayama.jpgEiichi Nakayama and Akiko Uenaka report in vivo depletion of CD8 T cells by administrating an anti-Lyt antibody. The method became widely used to dissect T cell responses in vivo.



Nakayama E, Uenaka A. Effect of in vivo administration of Lyt antibodies. Lyt phenotype of T cells in lymphoid tissues and blocking of tumor rejection. J Exp Med 1985 Feb 1; 161: 345-355. (PMID: 3871834) Download PDF
 

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1985
Major Discovery
TUMOR NECROSIS FACTOR FIRST DEMONSTRATED IN DISEASE PATHOGENESIS
Details
November 09, 1985
Major Discovery
TUMOR NECROSIS FACTOR FIRST DEMONSTRATED IN DISEASE PATHOGENESIS

1985-Bruce-Beutler.jpgBruce Beutler and Anthony Cerami provide the first demonstration of the role of tumor necrosis factor in the pathogenesis of disease.

Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effects of endotoxin. Science 1985 Aug 30; 229: 869-871. (PMID: 3895437) (Pillars)

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1985
Major Discovery
THE ROLE OF THE MHC MOLECULE IN ANTIGEN PROCESSING AND PRESENTATION ESTABLISHED
Details
November 09, 1985
Major Discovery
THE ROLE OF THE MHC MOLECULE IN ANTIGEN PROCESSING AND PRESENTATION ESTABLISHED

1982-Emil-Unanue.jpgEmil Unanue and colleagues demonstrate that a processed peptide can bind to an MHC molecule directly, establishing the role of the MHC molecule in antigen processing and presentation.
 



Babbitt BP, Allen PM, Matsueda G, Haber E, Unanue ER. Binding of immunogenic peptides to Ia histocompatibility molecules. Nature 1985 Sep 26; 317: 359-361. (PMID: 3876313) (Pillars)

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1985
Major Discovery
TGF-BETA IDENTIFIED AND CLONED
Details
November 09, 1985
Major Discovery
TGF-BETA IDENTIFIED AND CLONED

1985-TGF-beta.jpgTransforming growth factor beta (TGF-beta) is identified and cloned by Rik Derynck and colleagues.



Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB, Goeddel DV. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature 1985 Aug 22; 316: 701. (PMID: 3861940)
 

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1985
Major Discovery
THE CHARACTERIZATION OF THE FULL TCR COMPLEX AND THE TCR ZETA CHAIN DISCOVERED
Details
November 09, 1985
Major Discovery
THE CHARACTERIZATION OF THE FULL TCR COMPLEX AND THE TCR ZETA CHAIN DISCOVERED

1985-Richard-D-Klausner.jpgLarry Samelson, Richard D. Klausner, and associates report the characterization of the full TCR complex and discovery of the TCR zeta chain.


Samelson LE, Harford JB, Klausner RD. Identification of the components of the murine T cell antigen receptor complex. Cell 1985 Nov; 43: 223-231. (PMID: 3878228)

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1985
Major Discovery
CLONING OF T CELL SURFACE PROTEINS
Details
November 09, 1985
Major Discovery
CLONING OF T CELL SURFACE PROTEINS

1985-Richard-A-Axel.jpgResearchers in the laboratory of Richard A. Axel, including Leonard Chess and Dan Littman, clone the genes for the CD4[i] and CD8[ii] T cell surface proteins.
 



[i] Maddon PJ, Littman DR, Godfrey M, Maddon DE, Chess L, Axel R. The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family. Cell 1985 Aug; 42: 93-104. (PMID: 2990703)

[ii] Littman DR, Thomas Y, Maddon PJ, Chess L, Axel R. The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes. Cell 1985 Feb; 40: 237-246. (PMID: 3871356)

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1984
Major Discovery
T CELL RECEPTOR ALPHA AND BETA CHAINS CLONED
Details
November 09, 1984
Major Discovery
T CELL RECEPTOR ALPHA AND BETA CHAINS CLONED
Mark M. Davis, in collaboration with Steve Hedrick, and Tak Mak publish the first studies reporting on the cloning of the mouse TCR β-chain and the human TCR β-chain, respectively. Two months later, Mark M. Davis and colleagues, including CRI Fellow Nick Gascoigne, identify the TCR α-chain.

Hedrick SM, Cohen DI, Nielsen EA, Davis MM. Isolation of cDNA clones encoding for T cell-specific membrane-associated proteins. Nature 1984 Mar 8-14; 308: 149-153. (PMID: 6199676)

Hedrick SM, Nielsen EA, Kavaler J, Cohen DI, Davis MM. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature 1984 Mar 8-14; 308: 153-158. (PMID: 6546606)

Yanagi Y, Yoshikai Y, Leggett K, Clark SP, Aleksander I, Mak TW. A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature 1984 Mar 8-14; 308: 145-149. (PMID: 6336315)

Chien Y, Gascoigne NRJ, Kavaler J, Lee NE, Davis MM. Somatic recombinations in a murine T-cell receptor gene. Nature 1984 May 24-30; 309: 322-326. (PMID: 6328306)
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1984
Major Discovery
DISCOVERY USHERS IN NEW ERA OF CYTOKINE RESEARCH
Details
November 09, 1984
Major Discovery
DISCOVERY USHERS IN NEW ERA OF CYTOKINE RESEARCH
Charles Dinarello and colleagues clone IL-1, opening up the field of cytokine biology.

Auron PE, Webb AC, Rosenwasser LJ, Mucci SF, Rich A, Wolff SM, Dinarello CA. Nucleotide sequence of human monocyte interleukin-1 precursor cDNA. Proc Natl Acad Sci U S A 1984 Dec; 81: 7907-7911. (PMID: 6083565)
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1984
Major Discovery
CLINICAL EXPERIMENTS SHOW PROMISE OF T CELLS TO ATTACK TUMORS
Details
November 09, 1984
Major Discovery
CLINICAL EXPERIMENTS SHOW PROMISE OF T CELLS TO ATTACK TUMORS
Lloyd J. Old, Herbert F. Oettgen, and Alexander Knuth conduct the first clinical experiments demonstrating that T cells could be trained to recognize and attack an established tumor.

Knuth A, Danowski B, Oettgen HF, Old LJ. T cell-mediated cytotoxicity against malignant melanoma: analysis with IL-2-dependent T cell cultures. Proc Natl Acad Sci U S A 1984 Jun; 81: 3511-3515. (PMID: 6610177)

 
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1984
Major Discovery
FIRST HEAT SHOCK PROTEIN DISCOVERED AS A TUMOR REJECTION ANTIGEN
Details
November 09, 1984
Major Discovery
FIRST HEAT SHOCK PROTEIN DISCOVERED AS A TUMOR REJECTION ANTIGEN

1993-Pramod-K-Srivastava.jpgPramod Srivastava and M.R. Das identify the gp100 molecule as an individually specific tumor rejection antigen of a rat hepatoma. This molecule, belonging to the gp96 family, is the first heat shock protein identified as a tumor rejection antigen.
 



Srivastava PK, MR Das. The serologically unique cell surface antigen of Zajdela ascitic hepatoma is also its tumor-associated transplantation antigen. Int J Cancer 1984 Mar 15; 33: 417-422. (PMID: 6698641)
 

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1984
Major Discovery
FIRST RIGOROUS ADJUVANT TRIALS OF RECOMBINANT INTERFERONS FOR RESECTABLE MELANOMA COMMENCED
Details
November 09, 1984
Major Discovery
FIRST RIGOROUS ADJUVANT TRIALS OF RECOMBINANT INTERFERONS FOR RESECTABLE MELANOMA COMMENCED

1984-Edward-Creagan.jpgEdward Creagan and John M. Kirkwood commence the first rigorous adjuvant trials of recombinant interferons for resectable melanoma.



Kirkwood JM, Ernstoff MS, Davis CA, Reiss M, Ferraresi R, Rudnick SA. Comparison of intramuscular and intravenous recombinant alpha-2 interferon in melanoma and other cancers. Ann Intern Med 1985 Jul; 103: 32-36. (PMID: 4003987)

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1984
Field Milestone
INTERNATIONAL SOCIETY FOR THE BIOLOGICAL THERAPY OF CANCER FOUNDED
Details
November 09, 1984
Field Milestone
INTERNATIONAL SOCIETY FOR THE BIOLOGICAL THERAPY OF CANCER FOUNDED

1984-International-Society-for-the-Biological-Therapy-of-Cancer-founded.jpgThe human genes for tumor necrosis factor (TNF-alpha), first identified by Lloyd J. Old and Elisabeth A. Carswell in 1975, and LT (TNF-beta) are cloned.[i][ii]
 



[i] Gray PW, Aggarwal BB, Benton CV, Bringman TS, Henzel WJ, Jarrett JA, Leung DW, Moffat B, Ng P, Svedersky LP, … Nedwin GR. Nature 1984 Dec 20; 321: 721-724. (PMID: 6334807)

[ii] Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Coeddel DV. Humor tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 1984 Dec 20; 312: 724-729. (PMID: 6392892)

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1984
Major Discovery
IL-2 IDENTIFIED AS A GROWTH FACTOR FOR B CELLS
Details
November 09, 1984
Major Discovery
IL-2 IDENTIFIED AS A GROWTH FACTOR FOR B CELLS

1984-IL-2.pngResearchers demonstrate that IL-2 is also a growth factor for B cells.
 



Zubler RM, Lowenthal JW, Erard F, Hashimoto N, Devos R, MacDonald HR. Activated B cells express receptors for and proliferate in response to pure IL-2. J Exp Med 1984 Oct 1; 160: 1170-1183. (PMID: 6434689)

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1984
Major Discovery
ENGAGEMENT OF T CELL RECEPTOR ELEVATES CYTOPLASMIC CALCIUM IN T CELLS
Details
November 09, 1984
Major Discovery
ENGAGEMENT OF T CELL RECEPTOR ELEVATES CYTOPLASMIC CALCIUM IN T CELLS

1984-Arthur-Weiss.jpegArthur Weiss and colleagues demonstrate that T cell receptor engagement triggers elevation of cytoplasmic calcium in T cells.
 



Weiss A, Imboden J, Shoback D, Stobo J. Role of T3 surface molecules in human T-cell activation: T3-dependent activation results in an increase in cytoplasmic free calcium. Proc Natl Acad Sci U S A 1984 Jul; 81: 4169-4173. (PMID: 6234599) Download PDF
 

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1984
Major Discovery
CLONING OF SEVERAL CYTOKINES REPORTED
Details
November 09, 1984
Major Discovery
CLONING OF SEVERAL CYTOKINES REPORTED

1984-cytokine.jpgAt the 4th International Lymphokine Workshop, the cloning of several cytokines is reported, including: the first of three chains in the IL-2 receptor, IL-2R-alpha, by Warren Leonard and colleagues[i]; the first haematopoietic growth factor IL-3 (multi-CSF), by the laboratory of Ian G. Young in Australia[ii]; GM-CSF by Antony Burgess, Ashley Dunn, and Nicholas Gough at the LICR Melbourne Branch[iii]; M-CSF by Ernest Kawasaki and colleagues[iv]; and G-CSF by Lawrence Souza and colleagues[v] and, independently, by Shigekazu Nakata and colleagues.[vi]
 



[i] Leonard WJ, Depper JM, Crabtree GR, Rudikoff S, Pumphrey J, Robb RJ, Krönke, Svetlik PB, Peffer NJ, Waldmann TA. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature 1984 Oct 18-24; 311: 626-631. (PMID: 6090948)

[ii] Fung MC, Hapel AJ, Ymer S, Cohen DR, Johnson RM, Campbell HD, Young IG. Molecular cloning of cDNA for murine interleukin-3. Nature 1984 Jan 19-25; 307: 233-237. (PMID: 6420702)

[iii] Gough NM, Gough J, Metcalf D, Kelso A, Grail D, Nicola NA, Burgess AW, Dunn AR. Molecular cloning of cDNA encoding a murine haematopoietic growth regulator, granulocyte-macrophage colony stimulating factor. Nature 1984 Jun 28; 309: 763-767. (PMID: 6610831)

[iv] Kawasaki ES, Ladner MB, Wang AM, Van Arsdell J, Warren MK, Coyne MY, Schweickart VL, Lee MT, Wilson KJ, Boosman A...Mark DF. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science 1985 Oct 18; 230: 291-296. (PMID: 2996129)

[v] Souza LM, Boone TC, Gabrilove J, Lai PH, Zsebo KM, Murdock DC, Chazin VR, Bruszewski J, Lu H, Chen KK et. al. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science 1986 Apr 4; 232: 61-65. (PMID: 2420009)

[vi] Nakata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H, Ono M. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 1986 Jan 30; 319: 415-418. (PMID: 3484805)

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1984
Major Discovery
FIRST SINGLE CELL ANALYSIS OF LYMPHOCYTE PROLIFERATION REPORTED
Details
November 09, 1984
Major Discovery
FIRST SINGLE CELL ANALYSIS OF LYMPHOCYTE PROLIFERATION REPORTED

1984-Doreen-Cantrell.jpgDoreen Cantrell and Kendall A. Smith report the first single cell analysis of lymphocyte proliferation.



Cantrell DA, Smith KA. The interleukin-2 T-cell system: a new cell growth model. Science 1984 Jun 22; 224: 1312-1316. (PMID: 6427923)

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1984
Major Discovery
FIRST CLUE FOR MECHANISM OF ALLELIC EXCLUSION OF IG GENES PROVIDED
Details
November 09, 1984
Major Discovery
FIRST CLUE FOR MECHANISM OF ALLELIC EXCLUSION OF IG GENES PROVIDED

1984-Ursula-Storb.jpgKin Ritchie, Ralph Brinster, and Ursula Storb show that an IgL transgene inhibits rearrangement of endogenous IgL genes, providing the first clue for the mechanism of allelic exclusion of Ig genes.
 



Ritchie KA, Brinster RL, Storb U. Allelic exclusion and control of endogenous immunoglobulin gene rearrangement in k transgenic mice. Nature 1984 Dec 6; 312: 517-520. (PMID: 6438533)
 

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1984
Major Discovery
CLONING OF THE HUMAN P53 GENE
Details
November 09, 1984
Major Discovery
CLONING OF THE HUMAN P53 GENE
The human p53 gene is cloned.

Matlashewski G, Lamb P, Pim D, Peacock J, Crawford L, Benchimol S. Isolation and characterization of a human p53 cDNA clone: expression of the human p53 gene. EMBO J 1984 Dec 20; 3: 3257-3262. (PMID: 6396087) Download PDF
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1983
Major Discovery
NEW EXPERIMENTAL EVIDENCE FOR CANCER IMMUNOSURVEILLANCE
Details
November 09, 1983
Major Discovery
NEW EXPERIMENTAL EVIDENCE FOR CANCER IMMUNOSURVEILLANCE
Catherine Uyttenhove and Thierry Boon show that immune escape of mouse tumors is due to antigen-loss variants rather than immunosuppression, experimentally validating the concept of cancer immunosurveillance.

Uyttenhove C, Maryanski J, Boon T. Escape of mouse mastocytoma P815 after nearly complete rejection is due to antigen-loss variants rather than immunosuppression. J Exp Med 1983 Mar 1; 157: 1040-1052. (PMID: 6187879) Download PDF
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1983
Major Discovery
ZUR HAUSEN LINKS CERVICAL CANCER TO HPV
Details
November 09, 1983
Major Discovery
ZUR HAUSEN LINKS CERVICAL CANCER TO HPV

Harald-zur-Hausen.jpgHarald Zur Hausen identifies the human papillomavirus as the causative agent of cervical cancer, leading to the development of preventive vaccines for cervical cancer.



Durst M, Gissmann L, Ikenberg H, zur Hausen H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A 1983 June; 80: 3812-3815. (PMID: 6304740) Download PDF

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1983
Tools & Technologies
ELISPOT CREATED
Details
November 09, 1983
Tools & Technologies
ELISPOT CREATED
ELISPOT, a new method to measure antigen-specific T cell responses, is developed by Cecil Czerkinsky and Orjan Ouchterlony. ELISOT is a major tool used in clinical trial immune monitoring today.

Czerkinsky C, Nilsson L, Nygren H, Ouchterlony O, Tarkowski A. A solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of specific antibody-secreting cells. J Immunol Methods 1983 Dec 16; 65 (1-2): 109-121. (PMID: 6361139)
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1983
Awards & Honors
CRI'S COLEY AWARD GOES TO DISCOVERY OF SUPPRESSOR T CELLS
Details
November 09, 1983
Awards & Honors
CRI'S COLEY AWARD GOES TO DISCOVERY OF SUPPRESSOR T CELLS

1983-Richard-K-Gershon.jpgCRI presents the Coley Award to Richard K. Gershon for the identification of suppressor T cells.

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1983
Major Discovery
NEW DISCOVERY OF THE TCR PROTEIN
Details
November 09, 1983
Major Discovery
NEW DISCOVERY OF THE TCR PROTEIN
Ellis Reinherz and Stuart F. Schlossman report the identification of the TCR protein and are the first to link it to the CD3 complex.

Meuer SC, Fitzgerald KA, Hussey RE, Hodgdon JC, Schlossman SF, Reinherz EL. Clonotypic structures involved in antigen-specific human T cell function: Relationship to the T3 complex. J Exp Med 1983 Feb 1; 157: 705-719. (PMID: 6185617) Download PDF
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1983
CRI Milestone
CRI BEGINS FUNDING HIV AND AIDS RESEARCH
Details
November 09, 1983
CRI Milestone
CRI BEGINS FUNDING HIV AND AIDS RESEARCH
CRI begins funding HIV and AIDS research, making it one of the first private national health research organizations to dedicate funds to studying AIDS and the cancers associated with it.

CRI publication “Investing in Cancer Immunotherapy.”
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1983
Major Discovery
CAUSE OF AIDS DISCOVERED
Details
November 09, 1983
Major Discovery
CAUSE OF AIDS DISCOVERED

1983-Francoise-Barre-Sinoussi.jpgFrançoise Barré-Sinoussi, Jean-Claude Chermann, and Luc Montagnier isolate a new retrovirus, named lymphadenopathy associated virus (LAV, now known as human immunodeficiency virus, HIV), as the cause of AIDS.
 



Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983 May 20; 220: 868-871. (PMID: 6189183)
 

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1983
Major Discovery
CLONING OF IL-2Details
Details
November 09, 1983
Major Discovery
CLONING OF IL-2Details

1983-Tadatsugu-Taniguchi.jpgTadatsugu Taniguchi and collaborators report the cloning of IL-2.



Taniguchi T, Matsui H, Fujita T, Takaoka C, Kashmina N, Yoshimoto R, Hamuro J. Structure and expression of a cloned cDNA for human interleukin-2. Nature 1983 Mar 24; 302: 305-310. (PMID: 6403867)

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1983
Major Discovery
IDENTIFICATION OF T CELL ANTIGEN RECEPTOR (TCR)
Details
November 09, 1983
Major Discovery
IDENTIFICATION OF T CELL ANTIGEN RECEPTOR (TCR)

Philippa-Marrack.jpgA team of researchers including Philippa Marrack, John Kappler, and James P. Allison provides conclusive evidence for the identification of the T cell antigen receptor (TCR).
 



Kappler J, Kubo R, Haskins K, Hannum C, Marrack P, Pigeon M, McIntyre B, Allison J, Trowbridge I. The major histocompatibility complex-restricted antigen receptor on T cells in mouse and man: identification of constant and variable peptides. Cell 1983 Nov; 35: 295-302. (PMID: 6605199) Download PDF
 

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1983
Major Discovery
SCID MICE AS VALUABLE RESEARCH TOOLS DISCOVERED
Details
November 09, 1983
Major Discovery
SCID MICE AS VALUABLE RESEARCH TOOLS DISCOVERED

1983-Melvin-Bosma.jpgMelvin Bosma discovers a mouse strain with severe combined immune deficiency (SCID). Since SCID mice have no natural immunity and cannot reject tissue transplants, they have become valuable research tools for studying many diseases, including cancer and HIV.
 



Bosma GC, Custer RP, Bosma MJ. A severe combined immunodeficiency mutation in the mouse. Nature 1983 Feb 10; 301: 527-530. (PMID: 6823332)

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1983
Major Discovery
ENDOSOMES DISCOVERED
Details
November 09, 1983
Major Discovery
ENDOSOMES DISCOVERED

1983-Ira-Mellman.jpgIra Mellman and Ari Helenius discover endosomes, which soon emerge as key sites for antigen processing and peptide loading to MHC class II molecules.



General reference: Helenius et al, 1983, Trends in Biochemical Sciences 78: 245-250. (PMID:)

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1983
Major Discovery
MAJOR TECHNIQUE DISCOVERED TO STUDY GENE REGULATION IN NORMAL AND MALIGNANT CELLS
Details
November 09, 1983
Major Discovery
MAJOR TECHNIQUE DISCOVERED TO STUDY GENE REGULATION IN NORMAL AND MALIGNANT CELLS

1983-Ralph-Brinster.jpgRalph Brinster, Kin Ritchie, Ursula Storb, and colleagues show for the first time that mouse transgenes can consist entirely of endogenous mouse DNA, without viral sequences, to achieve perfect tissue- and stage-specific expression. This work is one basis for the use in the scientific community of transgenes as a major technique to study gene regulation in normal and malignant cells.
 



Brinster RL, Ritchie KA, Hammer RE, O’Brien RL, Arp B, Storb U. Expression of a microinjected immunoglobulin gene in the spleen of transgenic mice. Nature 1983 Nov 24-30; 306: 332-336. (PMID: 6417544)

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1983
Major Discovery
FIRST STUDY TO FIND THE FUNCTION OF A CANCER CAUSING GENE
Details
November 09, 1983
Major Discovery
FIRST STUDY TO FIND THE FUNCTION OF A CANCER CAUSING GENE

1983-Waterfield-M-D.jpgM.D. Waterfield and colleagues demonstrate that the sis oncogene of simian sarcoma virus encodes platelet-derived growth factor, the first study to find the function of a cancer causing gene.



Waterfield MD, Scrace GT, Whittle N, Stroobant P, Johnsson A, Wasteson A, Westermark B, Heldin CH, Huang JS, Deuel TF. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature 1983 Jul 7-13; 304: 35-39. (PMID: 6306471)

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1983
Major Discovery
EVIDENCE INDICATES MACROPHAGE ACTIVATING FACTOR AS A FORM OF INTERFERON GAMMA
Details
November 09, 1983
Major Discovery
EVIDENCE INDICATES MACROPHAGE ACTIVATING FACTOR AS A FORM OF INTERFERON GAMMA

2001-Robert-D-Schreiber.jpgRobert D. Schreiber, David H. Katz, and colleagues provide biochemical and biosynthetic evidence indicating that the macrophage activating factor (MAF) produced by the murine T cell hybridoma clone 24/G1, which primes macrophages for nonspecific tumoricidal activity, is a form of interferon gamma (IFN gamma).


 


Schreiber RD, Pace JL, Russell SW, Altman A, Katz DH. Macrophage-activating factor produced by a T cell hybridoma: physiochemical and biosynthetic resemblance to gamma-interferon. J Immunol 1983 Aug; 131: 826-832. (PMID: 6408190)

 

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1982
Major Discovery
INTERLEUKIN-4 DISCOVERED
Details
November 09, 1982
Major Discovery
INTERLEUKIN-4 DISCOVERED
The cytokine later named interleukin-4 (IL-4) is first described by William Paul and Maureen Howard at the National Institute of Allergy and Infectious Disease as a novel B cell growth factor, and by Peter Jackson, Ellen Vitetta, Peter Krammer, and Ellen Puré at the University of Texas Southwestern Medical Center as a differentiation factor that induces isotype switching to IgG1.

Howard M, Farrar J, Hilfiker M, Johnson B, Takatsu K, Hamaoka T, Paul WE. Identification of a T cell-derived B cell growth factor distinct from interleukin 2. J Exp Med 1982 Mar 1; 155: 914-923. (PMID: 6977612) Download PDF

Jackson P, Pure E, Vitetta E, Krammer P. T cell-derived B cell differentiation factor(s): effect on the isotype switch of murine B cells. J Exp Med 1982 Mar 1; 155: 734-748. (PMID: 7038025) Download PDF
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1982
Major Discovery
FIRST EXPERIMENT LEADING TO RITUXAN
Details
November 09, 1982
Major Discovery
FIRST EXPERIMENT LEADING TO RITUXAN

1997-rituxan.jpgRonald Levy reports the first successful treatment of a patient with a monoclonal antibody against the idiotype of a B cell lymphoma. This led to the development of Rituxan for the treatment of lymphoma, the first monoclonal antibody to be approved for cancer by the FDA.



Miller RA, Maloney DG, Warnke R, Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med 1982 Mar 4; 306: 517-522. (PMID: 6173751)

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1982
Major Discovery
LYMPHOKINE-ACTIVATED KILLER (LAK) CELLS DESCRIBED
Details
November 09, 1982
Major Discovery
LYMPHOKINE-ACTIVATED KILLER (LAK) CELLS DESCRIBED
Steven A. Rosenberg and colleagues first describe lymphokine-activated killer (LAK) cells.
Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med 1982 Jun 1; 155: 1823-1841. (PMID: 6176669) Download PDF
 
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1982
Major Discovery
NEW DISCOVERY IN ANTIGEN PROCESSING
Details
November 09, 1982
Major Discovery
NEW DISCOVERY IN ANTIGEN PROCESSING
Kirk Ziegler and Emil Unanue report that antigen processing requires acidic intracellular vesicles, establishing the involvement of the endosomal/lysosomal pathway in antigen processing.

Ziegler HK, Unanue ER. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to cells to T cells. Proc Natl Acad Sci U S A 1982 Jan; 79: 175-178. (PMID: 6798568) Download PDF
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1982
Major Discovery
PDF LINK BROKEN FIRST BIOCHEMICAL DESCRIPTION OF THE ΑΒ-T CELL RECEPTOR
Details
November 09, 1982
Major Discovery
PDF LINK BROKEN FIRST BIOCHEMICAL DESCRIPTION OF THE ΑΒ-T CELL RECEPTOR

1982-Allison-James.jpgJames P. Allison, Bradley W. McIntyre, and David Bloch report the first biochemical description of the αβ-T cell receptor.



Allison JP, McIntyre BW, Bloch D. Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. J Immunol 1982 Nov; 129: 2293. (PMID: 6181166) Download PDF

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1982
Major Discovery
NEW ANTIGENS RECOGNIZED BY CYTOTOXIC T LYMPHOCYTES
Details
November 09, 1982
Major Discovery
NEW ANTIGENS RECOGNIZED BY CYTOTOXIC T LYMPHOCYTES

1982-Thierry-Boon.jpgThierry Boon and colleagues show that immunogenic mutagenized tumor variants (tum) express new antigens recognized by cytotoxic T lymphocytes (CTLs).
 



Maryanski J, Boon T. Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. IV. Analysis of variant-specific antigens by selection of antigen-loss variants with cytolytic T cell clones. Eur J Immunol 1982 May; 12: 406-412. (PMID: 6178608)

Maryanski JL, Van Snick J, Cerottini JC, Boon T. Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. III. Clonal analysis of the syngeneic cytolytic T lympocyte response. Eur J Immunol 1982 May; 12: 401-406. (PMID: 6178607)

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1980
Major Discovery
THE EARLIEST RECOGNIZABLE T CELL PROGENITORS IDENTIFIED
Details
November 13, 1980
Major Discovery
THE EARLIEST RECOGNIZABLE T CELL PROGENITORS IDENTIFIED

1985-T-cell.jpgB.J. Fowlkes, Bonnie J. Mathieson, and colleagues identify CD4 and CD8 double-negative cells in the adult thymus as the earliest recognizable T cell progenitors.



Fowlkes BJ, Edison L, Mathieson BJ, Chused TM. Early T lymphocytes. Differentiation in vivo of adult intrathymic precursor cells. J Exp Med 1985 Sep 1; 162: 802–822. (PMID: 2863322) (Pillars) Download PDF

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1970
1979
Major Discovery
P53 DISCOVERED
Details
November 09, 1979
Major Discovery
P53 DISCOVERED
The product of the p53 tumor suppressor gene is discovered independently by several groups: Lionel Crawford and David Lane; Albert Deleo and Lloyd Old; and Arnold Levine. Of the discoveries, Drs. DeLeo and Old were the only the link the mutation of the protein to cancer in humans, rather than in experimental systems.
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1979
Major Discovery
ANTIBODIES USED TO SEPARATE DIFFERENT T CELL SUBSETS
Details
November 09, 1979
Major Discovery
ANTIBODIES USED TO SEPARATE DIFFERENT T CELL SUBSETS
Ellis Reinherz, Gideon Goldstein, and Stuart Schlossman report the separation of functional subsets of human T cells by a monoclonal antibody.

Reinhertz ER, Kung PC, Goldstein G, Schlossman SF. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A 1979 Aug; 76: 4061-4065. (PMID: 315070)
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1978
Major Discovery
FIRST CLINICAL STUDY OF INTERFERON FOR CANCER
Details
November 09, 1978
Major Discovery
FIRST CLINICAL STUDY OF INTERFERON FOR CANCER
CRI provides seed funding for the first clinical trial of interferon alpha in 14 cancer patients—the first human testing of a biological therapy for cancer—conducted by Jordan U. Gutterman at MD Anderson Hospital and Tumor Institute (now MD Anderson Cancer Center). 

“The award during the past year of $12,000 by the Cancer Research Institute to me for interferon studies has been extraordinarily important to me in getting the initial work off the ground. The money from the Cancer Research Institute allowed me to pay for patient expenses and incidentals related to the studies. Without the money, we would have had difficulty in the first phases of the study. We appreciate very much the Cancer Research Institute confidence in us and the board members should be fully aware of the importance of this award money.” – Jordan U. Gutterman, Letter to Helen Coley Nauts, September 13, 1978
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1978
Major Discovery
ENDOTOXIN-INDUCED CANCER DEATH DEPENDENT ON T CELLS
Details
November 09, 1978
Major Discovery
ENDOTOXIN-INDUCED CANCER DEATH DEPENDENT ON T CELLS
Michael J. Berendt and Robert J. North demonstrate that endotoxin-induced tumor regression is dependent on T cell-mediated immunity.
Berendt MJ, North RJ, Kirstein DP. The immunological basis of endotoxin-induced tumor regression: requirement for T-cell-mediated immunity. J Exp Med 1978 Dec 1; 148: 1550-1159. (PMID: 309921) Download PDF
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1977
Major Discovery
T CELL GROWTH FACTOR DISCOVERED
Details
November 09, 1977
Major Discovery
T CELL GROWTH FACTOR DISCOVERED
Francis W. Ruscetti, Doris Morgan, and Robert C. Gallo report the discovery of T cell growth factor (TCGF), later renamed interleukin-2 (IL-2) in mice, making it possible to grow and expand normal lymphocytes long term. The availability of TCGF made it possible to study cloned T cells with a single antigen specificity, leading to an understanding of how T cells recognize the TCGF/IL-2, to the identification of receptors for TCGF and antigens, and to the unanticipated identification of Th1- and Th2-polarized T cell types.

Ruscetti FW, Morgan DA, Gallo RC. Functional and morphologic characterization of human T cells continuously grown in vitro. J Immunol 1977 Jul; 119: 131-138. (PMID: 141483)
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1977
Treatment Approved
TAMOXIFEN APPROVED FOR BREAST CANCER
Details
November 09, 1977
Treatment Approved
TAMOXIFEN APPROVED FOR BREAST CANCER

Tamoxifen-tablets-used-to-008.jpgFDA approves tamoxifen, an anti-estrogen drug, for the treatment of breast cancer.

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1976
Major Discovery
MAJOR MECHANISM OF ANTIBODY DIVERSITY DISCOVERED
Details
November 09, 1976
Major Discovery
MAJOR MECHANISM OF ANTIBODY DIVERSITY DISCOVERED
Susumu Tonegawa discovers somatic recombination of immunoglobulin genes, the genetic principle for the generation of antibody diversity.

Hozumi N, Tonegawa S. Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. Proc Nat Acad Sci U S A 1976 Oct; 73: 3628. (PMID: 824647)

Brack C, Hirama M, Lenhard-Schuller R, Tonegawa S. A complete immunoglobulin gene is created by somatic recombination. Cell 1978; 15: 1-14. (PMID: 100225)
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1976
Tools & Technologies
NEW MODEL TO STUDY T CELL DEVELOPMENT
Details
November 09, 1976
Tools & Technologies
NEW MODEL TO STUDY T CELL DEVELOPMENT

Using mouse fetal organ culture techniques, John H. Robinson and John J.T. Owen show that functionally competent T cells could be generated within explanted thymic tissue under controlled conditions in vitro, paving the way for the study of mechanisms regulating T cell development.



Robinson JH, Owen JJT. Generation of T-cell function in organ culture of foetal mouse thymus. I. Mitogen responsiveness. Clin Exp Immunol 1977 Feb; 23: 347-354. (PMID: 139222) (Pillars)

 

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1975
CRI Milestone
CRI COLEY AWARD ESTABLISHED, FIRST AWARDS DINNER HELD
Details
November 09, 1975
CRI Milestone
CRI COLEY AWARD ESTABLISHED, FIRST AWARDS DINNER HELD

1975_awards-dinner_hotel-pierre.jpgCRI holds its 1st Awards Dinner, bestowing the inaugural William B. Coley Award in Cancer Immunology to 16 men and women named the “Founders of Tumor Immunology”: Garry I. Abelev, Edward A. Boyse, Edward J. Foley, Robert A. Good, Peter A. Gorer, Ludwik Gross, Gertrude and Werner Henle, Robert J. Huebner, Edmund Klein, Eva and Georg Klein, Donald L. Morton, Lloyd J. Old, Richmond T. Prehn, and Hans O. Sjogren. 
 
“From the time of William Coley and even earlier, there had been hints that at least some tumors were immunogenic, but the field of tumor immunology had become something of a red-light district: a seedy intellectual neighborhood of fantasy and wishful thinking, a landscape littered with the hulks of abandoned hypotheses and charred reputations. Several distinguished researchers had traversed this biological minefield with reputations intact, however, including Ludwik Gross, Edward Foley, the team of Richmond Prehn and Joan Main, George Klein, Peter Gorer, and Lloyd Old. Solid, imaginative, even heroic work emerged from their laboratories…” – Stephen A. Hall, A Commotion in the Blood

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1975
Major Discovery
TECHNIQUE MAKES POSSIBLE MONOCLONAL ANTIBODY PRODUCTION
Details
November 09, 1975
Major Discovery
TECHNIQUE MAKES POSSIBLE MONOCLONAL ANTIBODY PRODUCTION

Milstein-Kohler1982-copy-450x315.jpgGeorges Kohler and César Milstein develop hybridoma (‘somatic cell hybridization’) technology to generate monoclonal antibodies.


Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975 Aug 7; 256: 495. (PMID: 1172191)

 

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1975
Major Discovery
NATURAL KILLER CELL IDENTIFIEDClose
Details
November 09, 1975
Major Discovery
NATURAL KILLER CELL IDENTIFIEDClose
Rolf Kiessling, together with his two Ph.D. supervisors Eva Klein and Hans Wigzell at the Karolinska Institute in Stockholm, Sweden, names and demonstrates the unique properties of the natural killer (NK) cell in the mouse, establishing it as a distinct cell within the immune repertoire. Two months later, Mikael Jondal, also at the Karolinska Institute, reports the identification of the human NK cell.

Ronald Herberman also made key discoveries leading to the identification of this cell type.

Kiessling R, Klein E, Pross H, Wigzell H. “Natural” killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell. Eur J Immunol 1975 Feb; 5: 117-121. (PMID: 1086218)

Jondal M, Pross H. Surface markers on human B and T lymphocytes. Cytotoxicity against cell lines as a functional marker for lymphocyte subpopulations. Int J Cancer 1975 Apr 15; 15: 596-605. (PMID: 806545)

 
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1975
Field Milestone
THEORY OF CANCER IMMUNOSURVEILLANCE DEALT A BLOW
Details
November 09, 1975
Field Milestone
THEORY OF CANCER IMMUNOSURVEILLANCE DEALT A BLOW
Osias Stutman reports that “nude” mice, which were thought to lack immune system function, are no more likely to develop cancer than normal mice, suggesting that the immune system does not confer protection. The report discredits the theory of cancer immunosurveillance and, with it, the fundamental premise of tumor immunology.
Stutman O. Tumor development after 3-methylcholanthrene in immunologically deficient athymic-nude mice. Science 1974 Feb 8; 183: 534-536. (PMID: 4588620)
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1974
Treatment Approved
DOXORUBICIN APPROVED FOR CANCER
Details
November 09, 1974
Treatment Approved
DOXORUBICIN APPROVED FOR CANCER

doxorubicin.jpgFDA approves doxorubicin, an anthracycline antibiotic from Streptomyces bacteria, for cancer.

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1974
Major Discovery
DISCOVERY OPENS UP MAJOR NEW AVENUE TO STUDY B CELL DEVELOPMENT
Details
November 09, 1974
Major Discovery
DISCOVERY OPENS UP MAJOR NEW AVENUE TO STUDY B CELL DEVELOPMENT

0.jpgMartin Raff, Max Cooper, and J.J. Owen show that cells capable of producing antibodies are generated in the fetal liver of mice, demonstrating that the mouse fetal liver represents a mammalian equivalent to the avian bursa and providing an accessible in vitro system to study B cell development in the mouse.


Owen JJ, Cooper MD, Raff MC. In vitro generation of B lymphocytes in mouse foetal liver, a mammalian ‘bursa equivalent.’ Nature 1974 May 29; 249: 361-363. (PMID: 4546257)

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1974
Major Discovery
SYNTHETIC VIRAL MIMIC INCREASES BREAST CANCER SURVIVAL RATES
Details
November 09, 1974
Major Discovery
SYNTHETIC VIRAL MIMIC INCREASES BREAST CANCER SURVIVAL RATES
Fanny Lacour, at the Institut Gustav-Roussy, reports that the use of polyadenylic-polyuridylic acid (poly A:U) in combination with surgery increased breast cancer survival rates.
Lacour J, Lacour F, Spira A, Delage G, Michelson AM. [Trials of (poly A. poly U.) adjuvant immunotherapy in breast cancer treatment]. Bull Cancer 1974 Apr-Jun; 61: 275-280. (PMID: 4465011)
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1973
Major Discovery
DENDRITIC CELL DISCOVERED
Details
November 09, 1973
Major Discovery
DENDRITIC CELL DISCOVERED
Zanvil Cohn and Ralph Steinman discover the dendritic cell, a new immune cell that plays a crucial role in bridging innate and adaptive immunity, and further characterize it over the next several years. For this seminal work, Dr. Steinman is later awarded the 2011 Nobel Prize in Physiology or Medicine.

Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantification, tissue distribution. J Exp Med 1973 May 1; 137: 1142-1162. (PMID: 4573839)

 
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1973
CRI Milestone
NYCRI BECOMES CRI
Details
November 09, 1973
CRI Milestone
NYCRI BECOMES CRI
The New York Cancer Research Institute changes its name to the Cancer Research Institute.
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1972
Awards & Honors
NOBEL PRIZE FOR ANTIBODY DISCOVERIES
Details
November 09, 1972
Awards & Honors
NOBEL PRIZE FOR ANTIBODY DISCOVERIES

Nobel_Laureates_1972_Edelman_Porter.jpgRodney Porter and Gerard Edelman share the Nobel Prize in Physiology or Medicine for their discoveries about the chemical structure of antibody molecules. They deduced how antibodies have a constant region and two sites that bind to antigen. They were also able to explain how variations in the amino acid sequence of individual antibodies result in different binding shapes allowing them to bind to many different antigens. 

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1972
CRI Milestone
CRI ESTABLISHES VETERINARY CANCER UNIT
Details
November 09, 1972
CRI Milestone
CRI ESTABLISHES VETERINARY CANCER UNIT

cat_400x600.jpgCRI establishes the Veterinary Cancer Unit, led by William D. Hardy Jr., at the ASPCA Hospital, to deal with questions of leukemia and other cancers in animals. Among other discoveries, the unit made the significant initial finding that the leukemia virus of cats can be transferred from one cat to another.

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1971
Major Discovery
EVIDENCE FOR ROLE OF ANGIOGENESIS IN CANCER
Details
November 09, 1971
Major Discovery
EVIDENCE FOR ROLE OF ANGIOGENESIS IN CANCER

judah_folkman_md_1974.jpgJudah Folkman demonstrates that tumors express factors that encourage new blood vessel formation, or angiogenesis, suggesting that targeting these factors to slow or halt angiogenesis could be a viable strategy for cancer treatment. In 1989, the gene for vascular endothelial growth factor (VEGF) is identified, leading to the development of anti-angiogenesis treatments including bevacizumab (Avastin) for cancer.



Folkman J, Merler E, Abernathy C, Williams G. 1971. Isolation of a tumor factor responsible for angiogenesis. J Exp Med 133 (2): 275-88. (PMID: 4332371 )

 

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1971
CRI Milestone
CRI ESTABLISHES ITS POSTDOCTORAL FELLOWSHIP PROGRAM
Details
November 09, 1971
CRI Milestone
CRI ESTABLISHES ITS POSTDOCTORAL FELLOWSHIP PROGRAM
CRI establishes its Postdoctoral Fellowship Program, the Institute’s oldest formal grant program and the first program of its kind in the world, "for the support of qualified individuals who wish to receive training and experience in experimental or clinical cancer immunology."
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1971
Field Milestone
LUDWIG INSTITUTE FOR CANCER RESEARCH ESTABLISHED
Details
November 09, 1971
Field Milestone
LUDWIG INSTITUTE FOR CANCER RESEARCH ESTABLISHED
The Ludwig Institute for Cancer Research, which would become the world’s largest private cancer research institute, is established by Daniel K. Ludwig.
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1971
Field Milestone
NIXON SIGNS NATIONAL CANCER ACT
Details
November 09, 1971
Field Milestone
NIXON SIGNS NATIONAL CANCER ACT

richard-nixon-signs-national-cancer-act.jpgPresident Richard M. Nixon signs the National Cancer Act of 1971 on December 23. This Act authorizes the NCI Director to coordinate all activities of the National Cancer Program, to establish national cancer research centers, and to establish national cancer control programs.

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1971
Tools & Technologies
ELISA INVENTED
Details
November 09, 1971
Tools & Technologies
ELISA INVENTED
Eva Engvall and Peter Perlmann at Stockholm University invent the enzyme-linked immunosorbent assay (ELISA).

Engvall E, Perlmann P. Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry 1971 Sep; 8: 871-874. (PMID: 5135623)
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1970
Major Discovery
SUPPRESSOR T CELLS DESCRIBED
Details
November 09, 1970
Major Discovery
SUPPRESSOR T CELLS DESCRIBED

2007-T-cell.jpgRichard K. Gershon and K. (Kazunari) Kondo demonstrate a role of T cells, suppressor T cells, in the induction of immunological tolerance.



Gershon RK, Kondo K. Cell interactions in the induction of tolerance: The role of thymic lymphocytes. Immunology 1970 May; 18: 723-737. (PMID: 4911896)

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1970
Major Discovery
BCG CAUSES MELANOMA REGRESSIONS
Details
November 09, 1970
Major Discovery
BCG CAUSES MELANOMA REGRESSIONS

Donald-Morton.jpgDonald Morton and colleagues report the regression of melanoma tumors after administration of Bacillus Calmette-Guérin (BCG).



Morton DL, Eilber FR, Joseph WL, Wood WC, Trahan E, Ketcham AS. Immunological factors in human sarcomas and melanomas: a rational basis for immunotherapy. Ann Surg 1970 Oct; 172: 740-749. (PMID: 5272336)

 

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1970
Tools & Technologies
LEUKAPHERESIS INVENTED
Details
November 09, 1970
Tools & Technologies
LEUKAPHERESIS INVENTED

issac-djerassi.JPGIsaac Djerassi and colleagues invent leukocyte filtration (leukapheresis).



Djerassi I, Kim JS, Mitrakul C, Suvansri U, Ciesielka W. Filtration leukopheresis for separation and concentration of transfusable amounts of normal human granulocytes. J Med 1970; 1: 358-364. (PMID: 5286503)

 

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1960
1969
Major Discovery
INTERFERON CURES CANCER IN MICE
Details
November 09, 1969
Major Discovery
INTERFERON CURES CANCER IN MICE
Ion Gresser reports that interferon cures cancer in mice.

Commotion in the Blood, 156

Gresser I, Fontaine-Brouty-Boyé D, Bourali C, and Thomas M-T. A comparison of the efficacy of endogenous, exogenous, and combined endogenous-exogenous interferon in the treatment of mice infected with encephalomyocarditis virus. Proc Soc Exp Biol Med 1969 Jan; 30: 236-242. (PMID: 4302959)

Gresser I, Bourali C, Lévy, J-P, Fontaine-Brouty-Boyé D, and Thomas M-T. Increased survival in mice inoculated with tumor cells and treated with interferon preparations. Proc Nat Acad Sci U S A 1969 May 15; 63: 51-57. (PMID: 5257966)
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1969
CRI Milestone
LLOYD J. OLD JOINS THE CANCER RESEARCH INSTITUTE
Details
November 09, 1969
CRI Milestone
LLOYD J. OLD JOINS THE CANCER RESEARCH INSTITUTE
Lloyd J. Old becomes a scientific advisor to the Cancer Research Institute.
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1968
Tools & Technologies
NUDE MOUSE ESTABLISHED AS MAJOR RESEARCH TOOL
Details
November 09, 1968
Tools & Technologies
NUDE MOUSE ESTABLISHED AS MAJOR RESEARCH TOOL
Evagoras Michael Pantelouris reports that nude mice are congenitally athymic, leading to their widespread use in biomedical research.

Pantelouris EM. Absence of thymus in a mouse mutant. Nature 1968 Jan 27; 217: 370-371. (PMID: 5639157)

 
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1968
Major Discovery
FIRST CELL SURFACE DIFFERENTIATION ANTIGENS IDENTIFIED
Details
November 09, 1968
Major Discovery
FIRST CELL SURFACE DIFFERENTIATION ANTIGENS IDENTIFIED
Ted Boyse and Lloyd J. Old identify Ly antigens, originally named LY-A and LY-B and later called Ly-1, Ly-2, and Ly-3, the first cell surface antigens distinguishing normal cells of different lineages, introducing the concept cell surface antigens that could differentiate different cell types, later termed “differentiation antigens.” This discovery led directly to the CD (for “clusters of differentiation”) classification and the wide use of cell surface markers to distinguish and classify normal and malignant cells. Most notably, Dr. Old, with Eiichi Nakayama, discovered the LY-B/Ly-2 antigen, later renamed CD8. CD8 cells, often referred to as “killer” T cells, are one of the major cells of the adaptive immune response, and are capable of directly killing foreign or dangerous cells, including cancerous cells.
Boyse EA, Miyazawa M, Aoki T, Old LJ. Ly-A and Ly-B: two systems of lymphocyte isoantigens in the mouse. Proc R Soc Lond B Biol Sci 1968 Jun 11; 170: 175-193. (PMID: 4385242) (See also Hall monograph, chapter 3; Keating and Cambrosio. Biomedical Platforms: Realigning the Normal and the Pathological in Late-Twentieth Century Medicine.)
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1967
Major Discovery
NEW TREATMENT FOR ACUTE LYMPHOBLASTIC LEUKEMIA
Details
November 09, 1967
Major Discovery
NEW TREATMENT FOR ACUTE LYMPHOBLASTIC LEUKEMIA

Herbert-Oettgen.jpgHerbert OettgenCRI CONNECTIONCVC MEMBERSCIENTIFIC ADVISOR reports the first treatment of patients with acute lymphoblastic leukemia with L-asparaginase. These studies were based on experimental work published earlier that year by Lloyd Old and Ted Boyse on the treatment of lymphosarcoma in dogs with L-asparaginase.



Oettgen HF, Old LJ, Boyse EA, Campbell HA, Philips FS, Clarkson BD, Tallal L, Leeper RD, Schwartz MK, Kim JH. Inhibition of leukemias in man by L-asparaginase. Cancer Res 1967 Dec; 27: 2619-2631. (PMID: 5237354)

Old LJ, Boyse EA, Campbell HA, Brodey RS, Fidler J, Teller JD. Treatment of lymphosarcoma in the dog with L-asparaginase. Cancer 1967 Jul; 20: 1066-1070. (PMID: 5338446)

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1966
Awards & Honors
NOBEL PRIZE FOR CANCER CAUSES
Details
November 09, 1966
Awards & Honors
NOBEL PRIZE FOR CANCER CAUSES
Peyton Rous and Charles Higgins share the Nobel Prize for discoveries of tumor viruses and hormonal control of carcinoma, respectively.
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1965
Major Discovery
NEW INTERFERON IDENTIFIED
Details
November 09, 1965
Major Discovery
NEW INTERFERON IDENTIFIED
E. Frederick Wheelock discovers a new "interferon-like" virus inhibitor produced by immune cells (leukocytes) in response to phytohemagglutinin (PHA). This substance is now known as interferon gamma.

Wheelock EF. Interferon-like virus-inhibitor induced in human leukocytes by phytohemagglutinin. Science 1965 Jul 16; 149: 310-311. (PMID: 17533668) Access The PDF
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1965
CRI Milestone
COLEY'S TOXINS DISCREDITED
Details
November 09, 1965
CRI Milestone
COLEY'S TOXINS DISCREDITED
Coley’s Toxins is added to the American Cancer Society's Unproven Methods of Cancer Management. Although this classification was removed a decade later, since 1965, in order to conduct clinical studies of Coley's Toxins, investigators are required to submit an Investigational New Drug (IND) application with the FDA.
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1964
Major Discovery
FIRST VIRUS LINKED TO HUMAN CANCER
Details
November 09, 1964
Major Discovery
FIRST VIRUS LINKED TO HUMAN CANCER
Sir Anthony Epstein, Bert Achong, and Yvonne M. Barr describe a new herpesvirus, later named Epstein-Barr virus (EBV), in cultured Burkitt’s lymphoma cells. Later, with Gertrude and Werner Henle, Sir Anthony Epstein also isolates the agent in Burkitt’s lymphoma cells and reports that it is a new member of the human herpesvirus family, representing the first time a virus is linked to human cancer.

Epstein MA, Achong BG, Barr YM. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet 1964 Mar 28; 1: 702-703. (PMID: 14107961)

Epstein MA, Henle G, Achong BG, Barr YM. Morphological and biological studies on a virus in cultured lymphoblasts from Burkitt’s lymphoma. J Exp Med 1965 May 1; 121: 761-770. (PMID: 14278230)

Henle G, Henle W. Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol 1966 Mar; 91: 1248-1256. (PMID: 4160230)
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1963
Major Discovery
FIRST CANCER-SPECIFIC ANTIGEN IDENTIFIED
Details
November 09, 1963
Major Discovery
FIRST CANCER-SPECIFIC ANTIGEN IDENTIFIED
Garry Abelev and colleagues report the discovery of alpha fetoprotein (AFP, or oncofetal protein, OFA) as a serum marker for hepatoma and germ-cell tumors, the first cancer-specific antigen identified.
Abelev GI, Perova SD, Khramkova NI, Postnikova ZA, Irlin IS. Production of embryonal alpha-globulin by transplantable mouse hepatomas. Transplantation 1963 Apr; 1: 174-180. (PMID: 14010646)
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1963
Tools & Technologies
NEW ASSAY LAYS GROUNDWORK FOR FUTURE
Details
November 09, 1963
Tools & Technologies
NEW ASSAY LAYS GROUNDWORK FOR FUTURE
Niels K. Jerne and Albert Nordin develop the plaque assay for the enumeration of antibody-forming cells in vitro. The technology continues to form the basis for current immunological assays such as ELISPOT. Today ELISPOT, which measure antigen-specific T cell responses, is an indispensible tool for immunological monitoring in clinical trials of cancer vaccines and immunotherapies.

Jerne NK, Nordin AA. Plaque formation in agar by single antibody-producing cells. Science 1963 Apr 26; 140: 405. (PMID: 13957684)
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1962
Major Discovery
INTERFERON CAN ARREST CELL GROWTH
Details
November 09, 1962
Major Discovery
INTERFERON CAN ARREST CELL GROWTH
Kari Cantell and colleagues in the laboratory of Werner Henle demonstrate, for the first time, a non-antiviral cytotoxic effect of interferon. This suggested for the first time that interferon could kill cells that had not been virally infected, such as cancer cells.

Paucker K, Cantell K, Henle W. Quantitative studies on viral interference in suspended L cells. III. Effect of interfering viruses and interferon on the growth rate of cells. Virology 1962 Jun; 17: 324-334. (PMID: 14484446)
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1962
Treatment Approved
NEW CHEMOTHERAPY APPROVED
Details
November 09, 1962
Treatment Approved
NEW CHEMOTHERAPY APPROVED
FDA approves 5-fluorouracil (5-FU) for the treatment of cancer. 5-FU is still in use today, particularly in combinations, to treat several cancers.
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1961
Major Discovery
WHITE BLOOD CELLS MAKE INTERFERON
Details
November 09, 1961
Major Discovery
WHITE BLOOD CELLS MAKE INTERFERON
Ion Gresser reports that white blood cells called leukocytes make interferon.
Gresser I. Production of interferon by suspensions of human leukocytes. Proc Soc Exp Biol Med 1961 Dec; 108: 799-803. (PMID: 13901743) View Abstract
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1961
Treatment Approved
VINBLASTINE APPROVED FOR CANCER
Details
November 09, 1961
Treatment Approved
VINBLASTINE APPROVED FOR CANCER

1961-vinblastine-periwinkle.jpgThe U.S. Food and Drug Administration (FDA) approves vinblastine for the treatment of cancer. Vinblastine was first isolated from the Madagascar periwinkle.

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1960
Major Discovery
MORE EVIDENCE OF ANTI-TUMOR IMMUNITY
Details
November 09, 1960
Major Discovery
MORE EVIDENCE OF ANTI-TUMOR IMMUNITY
Building on the work of Richmond Prehn, George Klein, Hans-Olof Sjogren, Eva Klein, and Karl Erik Hellstrom at the Karolinska Institute report on mouse experiments that provide additional evidence that tumors can be recognized by the immune system and that immune responses are tumor-specific and protective. Also at the Karolinksa Institute, L. Révész reports on additional experiments providing evidence of tumor-specific antigens.

[i] Klein G, Sjogren HO, Klein E, Hellstrom KE. Demonstration of resistance against methlycholanthrene-induced sarcomes in the primary autochthonous host. Cancer Res 1960 Dec; 20: 1561-1572. (PMID: 13756652)

[ii] Révész L. Detection of antigenic differences in isologous host-tumor systems by pretreatment with heavily irradiated tumor cells. Cancer Res 1960; 20: 443-451.
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1960
Tools & Technologies
NEW WAY TO CULTURE IMMUNE CELLS
Details
November 09, 1960
Tools & Technologies
NEW WAY TO CULTURE IMMUNE CELLS
Peter Nowell shows that phytohemagglutinin (PHA) is critical to immune cell growth, offering a new technique to culture peripheral blood cells.

Nowell PC. Phytohemagglutinin: an initiator of mitosis in cultures of normal human leukocytes. Cancer Res 1960; 20: 462-466.

 
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1950
1959
Major Discovery
BCG SHOWS PROMISE AGAINST CANCER
Details
November 09, 1959
Major Discovery
BCG SHOWS PROMISE AGAINST CANCER
Lloyd Old and Baruj Benacerraf demonstrate that Bacillus Calmette-Guérin (BCG), the tuberculosis vaccine, inhibits tumor growth in mice. BCG is now widely used as a first line treatment for superficial bladder cancer.

Old LJ, Clarke DA, Benacerraf B. Effect of Bacillus Calmette Guerin infection on transplanted tumors in the mouse. Nature 1959 Jul 25; 184: 291-292. (PMID: 14428599)
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1958
Major Discovery
COMBINATION CHEMOTHERAPY PIONEERED
Details
November 09, 1958
Major Discovery
COMBINATION CHEMOTHERAPY PIONEERED
NCI researchers Emil Frei and James Holland and their colleagues pioneer the use of combination chemotherapy, in which multiple drugs with different mechanisms of action are used together to treat cancer. Partial and complete remissions, as well as prolonged survival, are obtained in children and adults with acute leukemia treated with combinations of 6-mercaptopurine and methotrexate.

Frei E III, Holland JF, Schneiderman MA, Pinkel D, Selkirk G, Freireich EJ, Silver RT, Gold GL, Regelson W. A comparative study of two regimens of combination chemotherapy in acute leukemia. Blood 1958 Dec; 13: 1126-1148. (PMID: 13596417) Access PDF
 
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1957
Major Discovery
INTERFERON DISCOVERED
Details
November 09, 1957
Major Discovery
INTERFERON DISCOVERED
Alick Isaacs and Jean Lindenmann discover interferon, a virus-fighting protein produced by animal cells. Eventually, three major types (I, II, and III) of interferon will be identified. In addition to fighting virus infections, interferons can also fight tumors.

Isaacs A, Lindenmann J. Virus interference. I. The interferon. Proc R Soc Lond Biol Sci 1957 Sep 12; 147: 258-267. (PMID: 13465720) Access PDF (reprinted in 1988 by CA: A Cancer Journal for Clinicians)
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1957
Major Discovery
PILLAR OF EARLY TUMOR IMMUNOLOGY
Details
November 09, 1957
Major Discovery
PILLAR OF EARLY TUMOR IMMUNOLOGY
Richmond T. Prehn and Joan Main develop inbred mouse strains to demonstrate specific cancer antigens.

“The history of attempts to immunize against cancer is one of long frustration. As a result of apparent failure during the past half century, it is current consensus that immune mechanisms probably will be of little use in the control of this disease.” – Richmond T. Prehn and Joan M. Main, “Immunity to Methylcholanthrene-Induced Sarcomas,” Journal of the National Cancer Institute 18: 769-78 (June 1957)

Prehn RT, Main JM. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst 1957 Jun; 18: 769-778. (PMID: 13502695) Access the PDF
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1957
Major Discovery
CANCER-CAUSING VIRUS DISCOVERED
Details
November 09, 1957
Major Discovery
CANCER-CAUSING VIRUS DISCOVERED
Charlotte Friend characterizes a murine leukemia virus, later named the Friend leukemia virus (FLV). The Friend leukemia virus is one of several discoveries leading to a resurgence in the virus theory of cancer in the 1960s and 1970s.
Friend C. The isolation of a virus causing a malignant disease of the hematopoietic system in adult Swiss mice. Proceedings of the American Association for Cancer Research 1956; 2: 106.

Friend C. Cell-free transmission in adult Swiss mice of a disease having the character of a leukemia. J Exp Med 1957; 105: 307-18. Access the PDF
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1956
Major Discovery
FIRST CURE FOR A SOLID TUMOR
Details
November 09, 1956
Major Discovery
FIRST CURE FOR A SOLID TUMOR
Roy Hertz and Min Chiu Li demonstrate that methotrexate treatment could cure choriocarcinoma, representing the first successful chemotherapy for a solid tumor.
 

Hertz R, Li MC, Spencer DB. Effect of methotrexate therapy upon choriocarcinoma and chorioadenoma. Proc Soc Exp Biol Med 1956 Nov; 93: 361-366. (PMID: 13379512)
 
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1955
Major Discovery
A NEW "NATURAL SELECTION" THEORY OF ANTIBODY FORMATION
Details
November 09, 1955
Major Discovery
A NEW "NATURAL SELECTION" THEORY OF ANTIBODY FORMATION
Niels K. Jerne publishes a new “natural selection” theory of antibody formation, marking the beginning of a series of discoveries over the following four years that would result in the development and eventual adoption of the clonal selection theory of antibody production by David Talmage and MacFarlane Burnet, transforming ideas on cellular immunity.
Jerne NK. The natural-selection theory of antibody formation. Proc Natl Acad Sci USA. 1955 Nov 15 ; 41: 849-57. (PMID: 16589759)
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1955
Major Discovery
A KEY ROLE IN ANTIBODY PRODUCTION IN BIRDS
Details
November 09, 1955
Major Discovery
A KEY ROLE IN ANTIBODY PRODUCTION IN BIRDS
Bruce Glick, Timothy S. Chang, and R. George Jaap demonstrate that the bursa of Fabricus in birds plays a key role in the ability to produce antibodies.
[i] Glick B, Chang TS, Jaap RG. The bursa of Fabricus and antibody production. Poultry Sci 1955; 35: 224-225.
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1954
CRI Milestone
CRI APPROVES FIRST GRANT
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November 09, 1954
CRI Milestone
CRI APPROVES FIRST GRANT
The New York Cancer Research Institute awards its first grant to Barbara Johnston, assistant professor of medicine at NYU-Bellevue Hospital, for research to identify the tumor destructive factors of Coley’s Toxins.

Johnston BJ. Clinical effects of Coley’s toxin. I. A controlled study. Cancer Chemother Rep 1962 Aug; 21: 19-41. (PMID: 14452139)

Johnston BJ, Novales ET. Clinical effect of Coley’s toxin. II. A seven-year study. Cancer Chemother Rep 1962 Aug; 21: 43-68. (PMID: 14452138)

 
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1953
CRI Milestone
CANCER RESEARCH INSTITUTE ESTABLISHED
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November 09, 1953
CRI Milestone
CANCER RESEARCH INSTITUTE ESTABLISHED
The New York Cancer Research Institute (now Cancer Research Institute)—the first organization dedicated exclusively to the treatment of cancer through the understanding and application of immunology—is founded by Helen Coley Nauts and Oliver R. Grace.
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1953
Treatment Approved
NEW CHEMOTHERAPIES APPROVED
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November 09, 1953
Treatment Approved
NEW CHEMOTHERAPIES APPROVED
FDA approves methotrexate, an antimetabolite derived from folic acid, and 6-mercaptopurine as anti-cancer drugs.
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1953
Major Discovery
STRUCTURE OF DNA DISCOVERED
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November 09, 1953
Major Discovery
STRUCTURE OF DNA DISCOVERED
James Watson and Francis Crick elucidate the structure of DNA (double helix). In their publication, they hint, understatedly, at the possible implications for genetic manipulation, writing, "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."

Watson JD, Crick FH. Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature 1953 Apr 25; 171: 737-738. (PMID: 13054692)
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1953
Major Discovery
TUMOR IMMUNOLOGY GETS "ON THE MAP"
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November 09, 1953
Major Discovery
TUMOR IMMUNOLOGY GETS "ON THE MAP"
Edward J. FoleyCRI CONNECTIONCOLEY AWARD, of the Schering Corp. in New Jersey, reports on a series of tumor transplantation experiments in inbred mice showing that the growth of a tumor transplant followed by its removal increased the mouse’s resistance to a second transplant of the same tumor, providing further evidence for the existence of tumor-specific antigens. According to Herbert Oettgen, these experiments “put tumor immunology on the map.”
Foley EJ. Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Research 1953 Dec; 13: 835-37. (PMID: 13116120) Commotion, 268
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1953
Major Discovery
BUILDING ON THE HYPOTHESIS OF "IMMUNOLOGICAL TOLERANCE"
Details
November 09, 1953
Major Discovery
BUILDING ON THE HYPOTHESIS OF "IMMUNOLOGICAL TOLERANCE"
Rupert Billingham, Leslie Brent, and Peter Medawar show that if cells from one mouse are introduced to the immune system of another mouse early in life, they would be accepted as “self” and not rejected, building on the hypothesis of “immunological tolerance” first proposed by Macfarlane Burnet in the late 1940s.
[i] Billingham RE, Brent L, Medawar PB. ‘Actively acquired tolerance’ of foreign cells. Nature. 1953 Oct 3 ; 172: 603-606. (PMID: 13099277)
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1953
Major Discovery
PASSIVE TRANSFER OF TRANSPLANTATION IMMUNITY
Details
November 09, 1953
Major Discovery
PASSIVE TRANSFER OF TRANSPLANTATION IMMUNITY
N. Avrion Mitchison demonstrates the passive transfer of transplantation immunity.
[i] Mitchison NA. Passive transfer of transplantation immunity. Nature 1953 Feb; 171: 267-268. (PMID: 13036857)
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1951
Major Discovery
EVIDENCE OF VIRAL TRANSMISSION OF CANCER
Details
November 09, 1951
Major Discovery
EVIDENCE OF VIRAL TRANSMISSION OF CANCER
Ludwik Gross shows that mouse leukemias can by transmitted by a virus.
Gross L. “Spontaneous” leukemia developing in C3H mice following inoculation in infancy, with AK-leukemic extracts, or AK-embryos. Proc Soc Exp Biol Med 1951 Jan; 76(1): 27-32. (PMID: 14816382) Gross L. The “vertical” transmission of mouse mammary carcinoma and chicken leukemia; its possible implications for human pathology. Cancer 1951 May; 3: 626-33. (PMID: 14839617) Commotion, Notes, p. 498, ref. Kevles, “Pursuing the Unpopular.”
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1950
Major Discovery
NEW CHEMOTHERAPY DEVELOPEDClose
Details
November 09, 1950
Major Discovery
NEW CHEMOTHERAPY DEVELOPEDClose
George Hitchings and Gertrude Elion synthesizes 6-mercaptopurine, an antimetabolite that will be used in the treatment of acute leukemia in children and adults.
Hitchings GH, Elion GB, Falco EA, Russell PB, Sherwood MB, Vanderwerff H. Antagonists of nucleic acid derivatives. I. The Lactobacillus casei model. J Biol Chem 1950; 183: 1-9.
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1940
1949
Treatment Approved
NITROGEN MUSTARD BECOMES THE FIRST CHEMOTHERAPY APPROVED BY THE FDA
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November 09, 1949
Treatment Approved
NITROGEN MUSTARD BECOMES THE FIRST CHEMOTHERAPY APPROVED BY THE FDA
Nitrogen mustard (mechlorethamine) becomes the first chemotherapy approved by the FDA.
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1948
Tools & Technologies
DEVELOPMENT OF CONGENIC MOUSE LINES
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November 09, 1948
Tools & Technologies
DEVELOPMENT OF CONGENIC MOUSE LINES
George Snell develops congenic mouse lines—animal strains that are isogenic except for one particular narrow and easily observable genetic expression—which were key in determining the major histocompatibility complex (MHC), the keystone of immunity.
[i] Snell GD. Methods for the study of histocompatibility genes. Journal of Genetics 1948 Oct; 49: 87-108. (PMID: 18893744) Milestones, 282-283.
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1948
Major Discovery
ANTIBODY PRODUCTION BY PLASMA CELLS
Details
November 09, 1948
Major Discovery
ANTIBODY PRODUCTION BY PLASMA CELLS
Astrid Fagraeus demonstrates antibody production by plasma cells, later to be identified as the products of B lymphocytes.
[i] Fagraeus A. Plasma cellular reaction and its relation to the formation of antibodies in vitro. Nature 1947 Apr 12; 159: 499. (PMID: 20295228)

[ii] Fagraeus A. The plasma cellular reaction and its relation to the formation of antibodies in vitro. J Immunol 1948 Jan; 58: 1-13. (PMID: 18897986)
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1946
Major Discovery
FURTHER EVIDENCE FOR THE H-2 COMPLEX
Details
November 09, 1946
Major Discovery
FURTHER EVIDENCE FOR THE H-2 COMPLEX
George Snell and Peter Gorer report that antigen II in mice is a major histocompatibility antigen, providing further evidence for the H-2 complex.
[i] Gorer PA, Lyman S, Snell GD. Studies on the genetic and antigenic basis of tumour transplantation: linkage between a histocompatiblity gene and ‘fused’ in mice. Proc Roy Soc Lond, Series B 1948; 135: 499-505.
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1945
Major Discovery
CATTLE TWINS DO NOT RESPOND TO EACH OTHER'S ANTIGENSClose
Details
November 09, 1945
Major Discovery
CATTLE TWINS DO NOT RESPOND TO EACH OTHER'S ANTIGENSClose
Ray Owen shows that cattle twins whose circulatory systems were connected in utero did not, after birth, respond each other’s antigens, suggesting a mechanism of immunological tolerance during development.
[i] Owen RD. Immunogenetic consequences of vascular anastomoses between bovine twins. Science. 1945 Oct 19; 102: 400-401. (PMID: 17755278)
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1942
Major Discovery
FIRST ADJUVANT DEVELOPED
Details
November 09, 1942
Major Discovery
FIRST ADJUVANT DEVELOPED
Jules Freund and Katherine McDermott develop the first adjuvant—a material that is not antigenic in itself but that can enhance the antigenic immune response—that could be used for any antige. The oil-based solution, called “complete Freund’s adjuvant,” established the principle of immune stimulation and provided immunologists with a broad “tool for inducing antibody formation and cellular immune responses to weakly antigenic substances and for producing models of autoimmune disorders.” Today, adjuvants are a fundamental component of cancer vaccination strategies.
Freund J, McDermott K. Sensitization to horse serum by means of adjuvants. Proceedings of the Society for Experimental Biology and Medicine 1942; 49: 548-553.
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1941
Tools & Technologies
FLUORESCENT ANTIBODY TECHNIQUE DEVELOPED
Details
November 09, 1941
Tools & Technologies
FLUORESCENT ANTIBODY TECHNIQUE DEVELOPED

1941-albert-coons.jpgAlbert Coons develops the fluorescent antibody technique, providing biologists and clinicians with a new imaging tool to enable the localization and identification of antigens, and later applied to quantitative immunoassays and to automatic differential cell sorters.


Coons AH, Creech HJ, Jones RN. Immunological properties of an antibody containing a fluorescent group. Proceedings of the Society of Experimental Biology and Medicine 1941; 47: 200-202. Milestones, 276-277.

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1930
1934
Field Milestone
NATIONAL CANCER INSTITUTE ESTABLISHED
Details
November 09, 1934
Field Milestone
NATIONAL CANCER INSTITUTE ESTABLISHED

1934-NCI-established.pngPresident Franklin D. Roosevelt signs legislation establishing the National Cancer Institute (NCI).

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1900
1909
Major Discovery
CANCER "IMMUNE SURVEILLANCE" HYPOTHESIS INTRODUCED
Details
November 09, 1909
Major Discovery
CANCER "IMMUNE SURVEILLANCE" HYPOTHESIS INTRODUCED

1909-paul-ehrlich.jpgPaul Ehrlich proposes that the immune system usually suppresses tumor formation, a concept that becomes known as the “immune surveillance” hypothesis. This theory would undergo several periods of acceptance and skepticism until 2001, when Robert Schreiber,Lloyd Old, and others provided firm experimental evidence of the phenomenon.


Ehrlich P. Über den jetzigen stand der karzinomforschung. Ned Tijdschr Geneeskd 1909; 5: 273-290.

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1908
Awards & Honors
EHRLICH, METCHNIKOFF SHARE NOBEL PRIZE
Details
November 09, 1908
Awards & Honors
EHRLICH, METCHNIKOFF SHARE NOBEL PRIZE
Paul Ehrlich, who made several seminal discoveries about the immune system and later proposed the theory of cancer immune surveillance, and Elie Metchnikoff, the first to provide evidence that cells provided protection against disease, share the Nobel Prize in Physiology or Medicine.
 
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1907
Major Discovery
COINS THE TERM IMMUNOCHEMISTRY
Details
November 09, 1907
Major Discovery
COINS THE TERM IMMUNOCHEMISTRY
Svante Arrhenius coins the term immunochemistry and hypothesizes that antigen-antibody complexes are reversible.
Arrhenius S. 1907. Immunohistochemistry. The application of the principles of physical chemistry to the study of the biological antibodies. Macmillan, New York. 309 p.
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1901
Major Discovery
SUCCESSFUL TRANSPLANTATION OF TUMORS IN ANIMALS
Details
November 09, 1901
Major Discovery
SUCCESSFUL TRANSPLANTATION OF TUMORS IN ANIMALS
In 1901-1903, Leo Loeb, in Canada and the United States, and Carl Jensen, at the Agriculture and Veterinary Institute in Copenhagen, demonstrate the successful transplantation of tumors in rats and mice, respectively.
[i] Loeb, L 1901. On Transplantation of Tumors. J Med Res 6: 28-38.

[ii] Loeb L. 1902. Further Investigations in Transplantation of Tumors. J Med Res 8: 44-73.

[iii] Leob L. 1902. Ueber Transplantationen eines Sarcoms der Thyroeidea bei einer weissen Ratte. Arch Pathol Anat Physiol 167: 188.

[iv] Jensen CO. 1902. Nogle Forsög med Kraeftevulster. Hopitalstidende 10: 489.

[v] Jensen CO. 1903. Experimentelle Undersǿgelser over Kraeft hos Mus (Experimental Researches on Cancer in the Mouse). Hospitalstidende 11: 549, 581.

[vi] Jensen CO. 1903. Experimentelle Untersuchungen über Krebs bei Maüsen. Centralbl Bakteriol Parasitenk Infektionskrankh 34: 28-34, 122-143.
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1901
Major Discovery
DISCOVERY OF BLOOD TYPES
Details
November 09, 1901
Major Discovery
DISCOVERY OF BLOOD TYPES
He also made major contributions to understanding how antibody molecules combine with antigen and of the specificity of antibodies at the chemical level, for which he was awarded the Nobel Prize for Physiology or Medicine in 1930.
Landsteiner, K. 1901. Ueber Agglutination-serscheinungen normalen menschliechen Blutes. Wiener Klinische Wochenenschrift 14: 1132-1134.
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1900
Major Discovery
MOLECULES MAY PLAY A KEY ROLE IN CANCER THERAPY
Details
November 09, 1900
Major Discovery
MOLECULES MAY PLAY A KEY ROLE IN CANCER THERAPY
Paul Ehrlich, in describing his side-chain theory of antibody formation, suggests that molecules that react with tumors could play a key role in cancer therapy.
Ehrlich P. 1900. On immunity with special reference to cell life. Proceedings of the Royal Society, London. Biology. 66: 424-448.
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1890
1894
Major Discovery
FURTHER EVIDENCE FOR HUMORAL IMMUNITY
Details
November 09, 1894
Major Discovery
FURTHER EVIDENCE FOR HUMORAL IMMUNITY

Richard Pfeiffer demonstrates the rapid killing of cholera bacteria in the cell-free serum of immunized guinea pigs (“Pfeiffer’s phenomenon”), providing further evidence for the humoral theory of immunity.
 



Pfeiffer R. Weitere Untersuchungen über das Wesen der Choleraimmunität und über specifisch baktericide Processe. Medical Microbiology and Immunology 1894; 18: 1-16.

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1893
Major Discovery
FIRST USE OF COLEY'S MIXED BACTERIAL TOXINS
Details
November 09, 1893
Major Discovery
FIRST USE OF COLEY'S MIXED BACTERIAL TOXINS

William-Coley_206x236.jpgWilliam B. Coley creates a filtered mixture of bacteria and bacterial lysates, composed of Streptococcus pyogenes and Bacillus prodigiosus, called “Coley’s Toxins,” to treat tumors. His first patient is a 21-year old man named John Ficken with a large inoperable tumor (likely a malignant sarcoma). After treatment with the toxins, Ficken had a complete remission, lasting until his death 26 years later of a heart attack.
 



Coley WB. May 1893. The Treatment of Malignant Tumors By Repeated Inoculations of Erysipelas: With A Report of Ten Original Cases. The American Journal of Medical Sciences. 1893; 10: 487-511. A Commotion in the Blood: Life, Death, and the Immune System, Stephen S. Hall.

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1891
Major Discovery
COLEY INAUGURATES AMERICAN CANCER IMMUNOTHERAPY
Details
November 09, 1891
Major Discovery
COLEY INAUGURATES AMERICAN CANCER IMMUNOTHERAPY

William B. Coley, M.D., a renowned surgeon at Memorial Hospital in New York, first attempts immune-modulating therapy for cancer with the inoculation of sarcoma patient Signor Zola with cultures of erysipelas.

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1890
Major Discovery
FIRST 'SERUM THERAPY'
Details
November 09, 1890
Major Discovery
FIRST 'SERUM THERAPY'

1890-shibasaburo-kitasato-and-emil-von-behring-206x136-1.jpgEmil von Behring and Shibasaburo Kitasato, in Robert Koch’s laboratory, find that injecting diphtheria toxin into animals produces a serum containing an anti-toxin that provides passive anti-diptheria immunity to people, introducing the use of serum as therapy and showing that immunity did not need to arise internally but could be transferred.


Behring E, Kitasato S. Ueber das Zustandekommen der Diptherie-Immunität und der Tetanus-Immunität bei Thieren. Deutsche Medizineische Wochenschrift 1890; 16: 1113-1114.

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Timeline of Progress

Since 1953, CRI and CRI scientists have played a major role in pioneering and accelerating the field of cancer immunotherapy.

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