Cancer Immunotherapy


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Leukemia is one of the major cancer types for which new immune-based cancer treatments are currently in development. This page features information on leukemia and immunotherapy clinical trials for leukemia patients, and highlights the Cancer Research Institute’s role in working to bring effective immune-based treatments to people with this type of cancer.

Urgent Need

Leukemia is a cancer of the bone marrow and blood and is classified into four main groups according to cell type and rate of growth: acute lymphocytic (ALL), chronic lymphocytic (CLL), acute myeloid (AML), and chronic myeloid (CML). The vast majority (91%) of leukemia cases are diagnosed in adults 20 years of age and older, among whom the most common types are CLL (35%) and AML (32%). Among children and teens, ALL is most common, accounting for 75% of pediatric leukemia cases.

In the U.S., over 60,1400 new cases of leukemia are expected in 2016, and more than 24,400 deaths. Survival rates vary substantially by leukemia subtype, ranging from a current 5-year relative survival rate of 25% for patients diagnosed with AML, to 84% for those with CLL. For those patients who relapse, or are not cured by existing approaches, newer treatments are badly needed. 

Current Treatment

Chemotherapy drugs, alone or in combination, are used to treat most types of leukemia. Some leukemia patients may require a hematopoietic stem cell transplant (HSCT) to fully eradicate their disease. In this procedure, high-dose chemotherapy, with or without radiation, is first used to eliminate the patient’s diseased bone marrow. Then, bone marrow stem cells from an immunologically matched donor (or from the patient’s own body) are given back to the patient. The transplanted stem cells then grow and repopulate the person’s bone marrow and blood with healthy cells.

Several targeted drugs (e.g., imatinib [Gleevec®], dasatinib [Sprycel®]) are effective for treating CML because they attack cells with the Philadelphia chromosome, the genetic abnormality that is the hallmark of this type of leukemia. Some of these drugs are also FDA-approved to treat a type of ALL involving the same genetic defect. For CLL that is CD20-positive, the monoclonal antibodies rituximab (Rituxan®), ofatumumab (Arzerra®), or obinutuzumab (Gazyva®) can be used in combination with chemotherapy as an initial treatment or as a treatment after disease has recurred. For CLL that is CD52-positive, the monoclonal antibody alemtuzumab (Campath®) may be used.

In 2014, the immunotherapy blinatumomab (Blincyto®) was approved for the treatment of Philadelphia chromosome-negative precursor B cell ALL that is refractory or has recurred. Blincyto is a special type of monoclonal antibody called a BiTE (see below).

Immunotherapy for leukemia

Several different types of immunotherapy are currently being explored for the treatment of leukemia. They fall into several broad categories, including adoptive cell therapy, monoclonal antibodies, and checkpoint inhibitors.

Adoptive Cell Therapy

Adoptive cell therapy is a type of immunotherapy in which immune cells are removed from a patient, grown or genetically modified in lab, and then given back to the patient, often in vastly increased numbers.

One particular adoptive cell therapy, called chimeric antigen receptor (CAR) T cell therapy, has been shown in early clinical trials to be particularly effective at treating leukemia. In CAR T cell therapy, T cells from a patient are removed and then genetically modified to express a protein receptor that recognizes a particular antigen found on leukemia cells. The receptor is called “chimeric” because it is a hybrid molecule made up of two different proteins (an antibody and a T cell receptor) joined together. Most existing CARs are designed to recognize a specific marker, called CD19, found on white blood cells called B cells. Both normal B cells and the cancerous B cells from which leukemias arise express CD19. 

In 2011, Carl H. June, M.D. (a CRI clinical investigator and member of the CRI Scientific Advisory Council), Michael Kalos, Ph.D. (a former CRI postdoctoral fellow and member of the CRI Scientific Advisory Council), and colleagues at the University of Pennsylvania School of Medicine achieved good clinical responses in patients with chronic lymphocytic leukemia (CLL), including two complete, durable clinical responses.[i] The approach has also been effective in treating acute lymphoblastic leukemia (ALL) in children and adults. In one trial, June and colleagues got 100% remissions in the pediatric group and 80%-90% remissions in the adult group. Many companies are now engaged in CAR T cell drug development.

CAR T cell therapies are currently being tested in clinical trials at various institutions:

  • University of Pennsylvania is enrolling adult patients with CLL (NCT01747486) and adult patients with ALL (NCT02030847, NCT02167360)
  • University of Pennsylvania and the Children’s Hospital of Philadelphia are enrolling pediatric and young adult patients with CD19-positive leukemia (NCT01626495)  
  • City of Hope Medical Center is enrolling adult patients with CLL, hairy cell leukemia, and prolymphocytic leukemia (NCT02153580); ALL (NCT02146924); AML (NCT02159495, not yet enrolling);  
  • Fred Hutchinson Cancer Research Center is enrolling adult patients with ALL, CLL, and hairy cell leukemia (NCT01865617)
  • Seattle Children’s Hospital is enrolling pediatric patients with CD19-positive leukemia (NCT02028455)
  • National Institutes of Health Clinical Center is enrolling pediatric and young adult patients with B cell leukemia (NCT01593696); and adult patients with B cell leukemia (NCT01087294)
  • Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute are enrolling pediatric and young adult patients with relapsed ALL (NCT01860937, NCT01430390)
  • Memorial Sloan Kettering Cancer Center is enrolling adult patients with CLL (NCT00466531, NCT01416974) and adult patients with ALL (NCT01044069)  
  • Baylor College of Medicine is enrolling both adult and pediatric patients with CLL and ALL (NCT01853631NCT00840853, NCT02050347)
  • University College London is enrolling pediatric and young adult patients with ALL (NCT01195480, NCT02443831, not yet enrolling)
  • Uppsala University is enrolling adult patients with B cell leukemia (NCT02132624)
  • Dana-Farber Cancer Institute is enrolling adult patients with AML (NCT02203825)

Monoclonal Antibodies

Monoclonal antibodies are molecules, generated in the lab, that target specific antigens on tumors. Many monoclonal antibodies are currently used in cancer treatment, and some appear to generate an immune response. Several monoclonal antibodies are currently FDA approved to treat some types of leukemia: rituximab (Rituxan), ofatumumab (Arzerra), and obinutuzumab (Gazyva) are approved to treat CLL that is CD20-positive; alemtuzumab (Campath) is approved to treat CLL that is CD52-positive; and blinatumomab (Blincyto) is approved to treat recurrent precursor B cell ALL that is Philadelphia chromosome-negative.

Blincyto is what’s called a bispecific T cell engager (BiTE), consisting of essentially 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 called CD19 on cancer cells; by bringing the two together, the BiTE facilitates cancer cell killing. In addition to its FDA-approved use for Philadelphia chromosome-negative ALL, Blinctyo is also being tested in patients with Philadelphia chromosome-positive ALL, where it has also shown promise.  

Several monoclonal antibodies are currently being tested in late-stage clinical trials: 

  • A phase III trial of blinatumomab (Blincyto) versus chemotherapy in adult patients with newly diagnosed Philadelphia chromosome-negative B cell ALL ( NCT02003222)
  • A phase III trial of blinatumomab (Blincyto) versus chemotherapy in younger patients with relapsed Philadelphia chromosome-negative B cell ALL (NCT02101853)
  • A phase III study of GDC-0199 plus rituximab versus bendamustine plus rituximab in patients with relapsed or refractory CLL (NCT02005471)
  • A phase III study of idelalisib in combination with either rituximab or chlorambucil for patients with previously untreated CLL (NCT01980875)
  • A phase III study of ublituximab in combination with ibrutinib compared to ibrutinib alone in adult patients with previously treated high-risk CLL (NCT02301156)
  • A phase III trial of moxetumomab pasudotox in adult patients with relapsed or refractory hairy cell leukemia (NCT01829711)
  • A phase III trial of bendamustine plus rituximab versus ibrutinib plus rituximab versus ibrutinib alone in older patients with untreated CLL (NCT01886872)
  • A phase III trial of obinutuzumab plus GDC-0199 versus obinutuzumab plus chlorambucil in patients with CLL (NCT02242942)
  • A phase III study of duvelisib (IPI-145) versus ofatumumab in patients with relapsed or refractory CLL (NCT02004522)
  • A phase III trial of ibrutinib in combination with obinutuzumab versus chlorambucil in combination with obinutuzumab in patients with treatment-naïve CLL (NCT02264574)

Checkpoint Inhibitors

A potentially promising avenue of treatment in leukemia is the use of immune checkpoint inhibitors. These drugs work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.

The following mid-stage studies are currently enrolling patients:

  • A phase II study of nivolumab (Opdivo®, an anti-PD-1 antibody) for patients with AML to eliminate residual disease and maintain remission after chemotherapy (NCT02275533)
  • A phase II trial of nivolumab (anti-PD-1) combined with ibrutinib for relapsed, refractory or high-risk untreated patients with CLL (NCT02420912)
  • A phase II study of pembrolizumab (Keytruda®, an anti-PD-1 antibody) in patients with relapsed or refractory CLL (NCT02332980)
  • A phase II study of CT-011 (anti-PD-1) in conjunction with a dendritic cell vaccine for patients with AML following chemotherapy-induced remission (NCT01096602)
  • A phase II trial of lirilumab (anti-KIR) combined with rituximab for relapsed, refractory or high-risk untreated patients with CLL (NCT02481297)

Go to our Clinical Trial Finder to find clinical trials of immunotherapies for leukemia that are currently enrolling patients.

CRI Contributions and Impact

Current and past CRI-funded studies on immunotherapy for leukemia include:

  • The first toxin-linked monoclonal antibody targeted toward anti-CD33 on leukemic blasts for acute myeloid leukemia (gemtuzumab ozogamicin, Mylotarg), was developed by Irving Bernstein, M.D. (1972-1974 postdoctoral fellow), and was approved by the FDA in 2000. Although it was withdrawn from the market in 2010, it gave rise to a host of other “antibody-drug conjugates” (ADC) such as T-DM1 from Genentech and SGN-35 (brentuximab vedotin), an ADC to CD30, approved by the FDA in 2011 for Hodgkin’s lymphoma, from Seattle Genetics.
  • CRI investigator Hiroyoshi Nishikawa, M.D., Ph.D., at Osaka University, is working to identify novel targets for immunotherapy against adult T cell leukemia/lymphoma (ATLL), a virus-related blood cancer that is resistant to conventional chemotherapies and is characterized by a poor prognosis. In one study, he found that several cancer-testis antigens, including NY-ESO-1, were highly expressed in ATLL and that they could be recognized by killer T cells, providing proof-of-principle for cancer-testis antigens as a novel and potentially promising target for ATLL immunotherapy.
  • CRI investigator Ryan Teague, Ph.D., at Saint Louis University School of Medicine focuses on understanding the mechanisms that inhibit T cell survival and efficacy following adoptive T cell immunotherapy for leukemia. He has shown that blockade of CTLA-4, PD-1, and LAG-3—three negative co-stimulatory pathways involved in curtailing anti-cancer immune responses—could restore anti-tumor activity in adoptively transferred T cells and result in durable and more effective anti-tumor immunity in advanced leukemia.
  • Over the course of his CRI postdoctoral fellowship Ryan Michalek, Ph.D., at Duke University Medical Center, has shown that the protein ERR-alpha (estrogen related receptor alpha) plays a key role in metabolism in activated T cells and is required for T cell proliferation and differentiation, as well as for the growth of leukemia cells. These findings have led to the hypothesis that ERR-alpha represents a master metabolic regulator for T cell activation and cancer cell growth. As such, it provides a novel target for regulating the immune response of healthy cells and decreasing the growth of leukemia and other cancers. These studies are among the first to identify a molecular target for modulating metabolism in vivo and suggest that ERR-alpha may be an important pharmaceutical target for the treatment of cancer and the modulation of immunity.
  • Discoveries by Malcolm A.S. Moore, D.Phil., and others at the Memorial Sloan Kettering Cancer Center about the origins of stem cells provided the scientific foundation for the development of bone marrow transplantation as a treatment for immune disorders, first begun in 1968, and, later, for leukemia and other blood cancers. His work has also contributed to the development of stem cell transplantation strategies that have shown success in curing otherwise untreatable blood cancers, including acute myeloid leukemia, lymphoma, and multiple myeloma. Today, his laboratory continues to undertake research on stem cells, with a particular focus on cancer stem cells in blood-related malignancies including leukemia and myeloproliferative disorders. In one project, he is undertaking a collaborative study with researchers at the Broad Institute/MIT and Harvard to identify and validate novel pharmacologic agents that impact leukemia stem cells. To date, the group has screened 17,000 compounds and identified a panel of 14 that selectively target leukemia stem cells and do not kill normal stem cells. Of these, two were particularly effective and demonstrated high toxicity against leukemia stem cells while sparing normal stem cells, making them highly attractive candidates for further study. Dr. Moore is continuing to characterize these compounds and conduct the necessary preclinical studies to lay the groundwork for testing these agents in human clinical trials.
  • Paola Betancur, Ph.D., is a CRI-funded postdoctoral fellow in the laboratory of Irving L. Weissman, M.D., an internationally recognized expert on stem cells and cancer stem cells, at Stanford University School of Medicine. In her project, she is working to validate and test therapeutic strategies targeting the CD47 protein to treat cancer. CD47 is a cell-surface protein that provides a “don’t eat me” signal to macrophages, a type of white blood cell that engulfs and digests dead and harmful cells. By increasing the production of CD47, cancer cells have the ability to evade the immune system. Preliminary studies have shown that AML stem cells produce higher levels of CD47 than normal healthy cells, and that treatment with antibodies to block CD47 allows the immune system to destroy AML cells without harming healthy cells. In her project, Dr. Betancur is working to identify the regulatory proteins that form part of the “switch” responsible for the upregulation of CD47 in cancer stem cells. The results of her project will help scientists develop novel therapies to target the regulatory proteins that cause CD47 overproduction in leukemia and other cancer stem cells, with the goal of restoring immunosurveillance and enabling the immune system to recognize and destroy these aberrant cancer cells.
  • Maria P. Frushicheva, Ph.D., a CRI postdoctoral fellow in the Department of Chemical Engineering at Massachusetts Institute of Technology, is investigating the role of two signaling proteins, ZAP-70 and Syk, in the progression of B cell chronic lymphocytic leukemia (CLL). She is using a combination of computational models and laboratory experiments to elucidate the mechanism of action of these proteins and their role in cancer progression. In her first year of research, she has found that cancer progression is correlated with the amount of ZAP-70 and Syk proteins present in cells, and she is now working to identify the reasons for these associations. The results of her research will help uncover additional targets for immunotherapies directed at components of these signaling pathways. 

  • Bradley Wayne Blaser, M.D., Ph.D., of Boston Children’s Hospital, is the studying the factors that control blood cell development, with the goal of improving immunotherapies for patients with leukemia. Hematopoietic stem cell transplantation (HSCT), also known as bone marrow transplantation, is an aggressive treatment for patients with high-risk or relapsed leukemia. Patients who receive HSCT receive high doses of chemotherapy, with or without radiation, followed by infusion of hematopoietic stem cells (HSCs)—rare cells that reside within the bone marrow and are capable of producing all varieties of blood cells. Despite this aggressive treatment, only a minority of patients can be cured of their disease. The key to improving HSCT lies in understanding how HSCs “engraft” or lodge in their bone marrow niche. Dr. Blaser is using the zebrafish as a model system to learn more HSC engraftment. His studies have uncovered a novel role for molecules called CXCR1 and IL-8 in this process. Ultimately this knowledge may be useful in developing drugs to help people undergoing HSCT.

Updated August 2015

Sources: American Cancer Society Cancer Facts & Figures 2016; GLOBOCAN 2012;; CRI grantee progress reports and other CRI grantee documents

[i] 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)


Leukemia News & Stories

Reviewed By:

John C. Byrd, M.D.
John C. Byrd, M.D.
D. Warren Brown Chair of Leukemia Research and Professor, The Ohio State University

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