Our Strategy & Impact

Our Accomplishments

We are proud not only of our long history of scientific excellence and discovery that has helped many cancer patients over the past six decades, but also of our ability to innovate our approach to funding and research to achieve the most impact with our donor-supported resources. Many of the successful results that have been seen in cancer immunotherapy are based on the research discoveries made by CRI scientists. Here are some of those landmark achievements:

Review of Major Discoveries and Accomplishments

  • In 1996, CRI Scientific Advisory Council director James P. Allison, Ph.D., and Matthew F. Krummel, Ph.D., a CRI investigator award recipient, established checkpoint blockade as a powerful new approach to cancer immunotherapy, by showing that an antibody which blocked the activity of a receptor on T cells called CTLA-4 could enhance tumor immunity[i]. This work led directly to clinical trials and paved the way for the FDA approval in 2011 of Yervoy® (ipilimumab), the first treatment shown to extend the lives of patients with advanced melanoma.
  • Chimeric antigen receptor (CAR) technology, a form of adoptive T cell therapy, was made possible by decades of research by CRI scientists, including Scientific Advisory Council members Carl H. June, M.D., and Michael Kalos, Ph.D., who was also a CRI postdoctoral fellow, and CRI postdoctoral fellow Isabelle Rivière, Ph.D. CAR T cell therapy has achieved complete responses in 90% of patients with leukemia, and is being tested in several cancers.[ii],[iii],[iv]
  • As a scientist at Dendreon, former CRI postdoctoral fellow Curtis Ruegg, Ph.D., helped to bring the first dendritic cell-based cancer vaccine—Provenge® (sipuleucel-T), for prostate cancer—to the clinic. It was approved by the FDA in 2010.[v]
  • In 1999, CRI awarded the first of several grants to Ian H. Frazer, M.D., FRCPA, for work on virus-like particles (VRP)-based papillomavirus vaccines. This work was crucial to the development of Gardasil®, the first preventive vaccine against cervical cancer, approved by the FDA in 2006. Gardasil now protects against nine types of HPV that cause approximately 90% of all cases of cervical cancer worldwide.
  • In 1993, Pramod Srivastava, M.D., Ph.D., a former CRI fellow and member of the Scientific Advisory Council, identified a novel ‘heat shock protein’ mechanism in cells and developed ways to exploit it for vaccine therapy. This technology led to the development of the Oncophage vaccine for kidney cancer, which became the world’s first therapeutic cancer vaccine to be approved for market, by the Russian Ministry of Public Health in April 2008. The vaccine is also in clinical trials in the U.S. for brain cancer.
  • In 2002, two studies, by CRI investigator Cassian Yee, M.D., and by CRI fellow Mark Dudley, Ph.D., showed for the first time that adoptive T cell therapy for patients with advanced melanoma using in vitro-expanded T cells can cause tumor regressions[vi],[vii]. In 2006, Dudley and colleagues showed that T cells genetically engineered to contain specific T cell receptors can be used to treat patients with melanoma, bypassing the need to expand tumor-specific T cells from patients[viii].
  • In 2001, CRI Scientific Advisory Council associate director Robert D. Schreiber, Ph.D., along with former CRI scientific director Lloyd J. Old, M.D., CRI fellow Hiroaki Ikeda, M.D., Ph.D., and Mark J. Smyth, Ph.D., proved the validity of the immunosurveillance concept, which says that the immune system protects against cancer, by showing that mice lacking interferon-gamma and perforin, two molecules expressed on CD8+ T cells that are central in cell-killing, have increased susceptibility to lymphomas. These scientists further established the theory of immunoediting to describe the immune system’s role in both combatting cancer and sculpting its evolution[ix],[x],[xi].
  • In 2000, Louis M. Staudt, M.D., Ph.D., a CRI investigator, and colleagues used DNA microarrays to conduct a systematic characterization of gene expression in diffuse large B cell lymphomas (DLBCL), identifying two molecularly distinct forms of DLBCL. Their results demonstrated that the molecular classification of tumors on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer[xii].
  • In 1993, CRI researchers Drew Pardoll, M.D., Ph.D., Glenn Dranoff, M.D., Elizabeth Jaffee, M.D., Hyam Levitsky, M.D., and colleagues showed that a vaccine composed of tumor cells irradiated and genetically modified to produce immune system growth factor GM-CSF could induce potent, specific, and long-lasting anti-tumor immunity in mice. This work led to the therapeutic cancer vaccine GVAX[xiii]. In 2014, the FDA designated GVAX given with another immunotherapy, CRS-207, as a “Breakthrough Therapy” for pancreatic cancer.
  • CRI postdoctoral fellow Xin-Yuan Fu, Ph.D., was a co-discoverer of the STAT gene family in 1992[xiv]. The discovery of the STAT family of proteins and their signaling pathway (called JAK-STAT) is known now as a major pathway involved in immunity, development, and cancer. Novel medicines interfering with JAK-STAT have since been approved for the treatment of numerous diseases.
  • CRI scientists have identified and characterized numerous cancer antigens that are used in vaccines and other targeted immunotherapies to direct the immune system against cancer. Coley Award winner Thierry Boon, Ph.D., and Scientific Advisory Council member and CRI investigator Alexander Knuth, M.D., were instrumental in discovering the first tumor-specific antigen, called MAGE, in 1991[xv].
  • In 1985, former CRI postdoctoral fellow Henry Erlich, Ph.D., and Kary Mullis, Ph.D., invented the polymerase chain reaction (PCR), which allows scientists to vastly amplify small amounts of DNA, and which has revolutionized molecular biology and medicine[xvi],[xvii].
  • CRI funded Alvaro Morales, M.D., who, in 1980, demonstrated that Bacillus Calmette-Guérin (BCG) is effective in the prevention of recurrence of invasive bladder cancer[xviii]. The FDA approved the use of BCG for superficial bladder cancer in 1990, becoming the standard therapy for the treatment of early-stage bladder cancer.
  • The p53 tumor suppressor gene, the gene most frequently mutated in human cancers, was discovered independently in 1979 by several groups of researchers, including CRI fellow David Lane, Ph.D., CRI fellow Albert DeLeo, Ph.D., and former CRI scientific director Lloyd J. Old, M.D. [xix],[xx]
  • In 1978, CRI provided seed funding to Jordan Gutterman, M.D., for the first significant trial of interferon alpha in human cancer patients—the first human testing of a biological therapy for cancer. The study paved the way for the FDA approval of this treatment in 1986 for leukemia[xxi].
  • The natural killer (NK) cell, an important cell of the innate immune system that fights virally infected and cancerous cells, was discovered in 1975 by CRI postdoctoral fellow Rolf Kiessling, M.D., Ph.D.[xxii]

Major Program Accomplishments

  1. Through our postdoctoral fellowship program, established in 1971, we have supported the continued professional training and early scientific work of nearly 1,300 young immunologists, ensuring a steady stream of talent into the field.
  1. In 2001, CRI, together with Ludwig Cancer Research, established the Cancer Vaccine Collaborative (CVC), a coordinated global network of investigators who collaborate on designing and implementing clinical trials of immunotherapies. Since then, the network has conducted nearly 70 early phase clinical trials of promising immunotherapies, and has produced a breadth of knowledge on the immunological and clinical effects of cancer immunotherapies.
  1. In 2012, we launched the Clinical Accelerator, a venture philanthropy program designed to speed the development of cancer immunotherapies by facilitating research collaboration between biopharma companies and academic cancer researchers. In three years, the Clinical Accelerator has secured access to more than 30 highly promising immunotherapies.
  1. Our Cancer Immunotherapy Consortium is a “think tank” which convenes the major stakeholders from academia, industry, regulatory bodies, and patient groups who share a common interest in promoting immunotherapy research and development. Accomplishments include: new guidelines for minimal reporting requirements for studies using immunological assays, harmonized guidelines for conducting immunological assays, and the development of improved criteria for monitoring the effectiveness of cancer immunotherapies in clinical trials.
  1. In 2014, CRI launched TheAnswerToCancer.org, the first-of-its-kind resource for patients and caregivers interested in learning about cancer immunotherapy across numerous tumor types. It provides an accessible overview of the science behind cancer immunotherapy, detailed information about cancer immunotherapy clinical trials, and voices from the cancer immunotherapy community.
  1. In 2013, CRI established Cancer Immunotherapy Month in June to raise awareness of cancer immunotherapy and its potential to transform cancer treatment in our lifetimes.

Thanks to donor support, we are able to continue advancing the highest quality science and fostering successful development of new immune-based cancer treatments.

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

[ii] 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)

[iii] 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)

[iv] 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)

[v] Patent#: U.S. 5,976,546; Patent#: U.S. 6,080,409; Patent#: U.S. 6,210,662; Patent#: U.S. 6,812,023; Patent#: U.S. 7,414,108.

[vi] 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)

[vii] 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. Report, Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002 Oct 25; 298: 850-854. (PMID: 12242449)

[viii] 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)

[ix] 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)

[x] 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)

[xi] 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)

[xii] Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J, Jr., Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM. 2000. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000 Feb 3; 403 (6769): 503-11. (PMID: 10676951)

[xiii] 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)

[xiv] 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 transduction. Proc Natl Acad Sci U S A 1992 Aug 15; 89: 7840-7843. (PMID: 1502204)

[xv] van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 1991 Dec 13; 254: 1643-1647. (PMID: 1840703)

[xvi] 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)

[xvii] 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)

[xviii] Morales A. Treatment of carcinoma-in-situ of the bladder with BCG. Cancer Immunol Immunother 1980; 9: 69.

[xix] Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature 1979 Mar 15; 278: 261-263. (PMID: 218111)

[xx] DeLeo AB, Jay G, Appella E, Dubois GC, Law LW, Old LJ. Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc Natl Acad Sci U S A 1979 May; 76: 2420-2424. (PMID: 221923)

[xxi] Gutterman JU, Blumenschein GR, Alexanian R, Yap HY, Buzdar AU, Cabanillas F, Hortobagyi GN, Hersh EM, Rasmussen SL, Harmon M, Kramer M, Pestka S. Leukocyte interferon-induced tumor regression in human metastatic breast cancer, multiple myeloma, and malignant lymphoma. Ann Intern Med 1980 Sep; 93: 399-406. (PMID: 6159812)

[xxii] 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)


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