Cancer Immunotherapy


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 cancer treatments to people with leukemia.

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.

Over 350,000 new cases of leukemia are expected in 2014, and more than 265,000 deaths. Survival rates vary substantially by leukemia subtype, ranging from a current 5-year relative survival of 24% for patients diagnosed with AML to 79% for those with CLL. Advances in treatment have resulted in a dramatic improvement in survival over the past three decades for most types of leukemia. In patients who fail, however, more treatments are needed.

Current Treatment

Chemotherapy is used to treat most types of leukemia. Various anti-cancer drugs are used, either in combination or as single agents. Several targeted drugs (e.g., imatinib [Gleevec]) 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, rituximab (Rituxan) can be used in combination with chemotherapy as an initial treatment or as a treatment after disease has recurred.

Immunotherapies in Development

One particular immunotherapy, 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 not naturally found on T cells. The genetically modified T cells are then put back into the patient so his or her immune system can begin fighting the cancer.

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 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, including Novartis Pharmaceuticals, Juno Therapeutics, Cellectis/Pfizer, Kite Pharma, and Lion Biotechnologies.

Organizations enrolling patients on CAR T cell therapies include:

  • University of Pennsylvania, where they are enrolling adult patients with chronic lymphocytic leukemia (NCT01747486) and adult patients with acute lymphocytic leukemia (NCT02030847)
  • University of Pennsylvania and the Children’s Hospital of Philadelphia are enrolling pediatric and young adult patients with leukemia (NCT01626495)
  • City of Hope Medical Center, where they are enrolling adult patients with chronic lymphocytic leukemia, hairy cell leukemia, and prolymphocytic leukemia (NCT02153580, not yet enrolling); acute lymphocytic leukemia (NCT02146924, not yet enrolling); acute myeloid leukemia (NCT02159495, not yet enrolling); acute lymphocytic leukemia (current or in remission), chronic lymphocytic leukemia, and hairy cell leukemia (NCT02051257); and hairy cell leukemia (NCT01815749)
  • Fred Hutchinson Cancer Research Center, where they are enrolling adult patients with acute lymphoblastic leukemia, chronic lymphocytic leukemia, and hairy cell leukemia (NCT01865617)
  • Seattle Children’s Hospital, where they are enrolling pediatric patients with leukemia (NCT02028455) and pediatric and adult patients with leukemia (NCT01683279)
  • National Institutes of Health Clinical Center, where they are enrolling adult patients with chronic lymphocytic leukemia (NCT00924326); pediatric and young adult patients with leukemia (NCT01593696); and adult patients with leukemia (NCT01087294)
  • Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute, where they are enrolling pediatric and young adult patients with relapsed acute lymphoblastic leukemia (NCT01860937, NCT01430390)
  • Memorial Sloan Kettering Cancer Center, where they are enrolling adult patients with chronic lymphocytic leukemia (NCT00466531, NCT01416974) and adult patients with acute lymphoblastic leukemia (NCT01044069)
  • Baylor College of Medicine, where they are enrolling both adult and pediatric patients with chronic lymphocytic leukemia and acute lymphocytic leukemia (NCT01853631, NCT00586391, NCT00840853, NCT02050347)
  • University College London, where they are enrolling pediatric and young adult patients with acute lymphoblastic leukemia (NCT01195480)

In addition, there are several checkpoint blockades and monoclonal antibodies that have shown promise in improving survival and have moved into late-phase clinical trials. These include:

  • inotuzumab ozogamicin, an anti-CD22 antibody being developed by Pfizer, is in phase III trials for acute lymphoblastic leukemia (NCT01564784)
  • blinatumomab (AMG 103), a bi-specific antibody, called a bi-specific T cell engager (BiTEs), which targets the CD19 antigen on B cells. It is being tested for adult acute lymphoblastic leukemia in a phase III trial (NCT02013167, NCT02003222) and pediatric acute lymphoblastic leukemia in a phase III trial (NCT02101853, not yet recruiting)
  • mogamulizumab is an anti-CCR4 antibody, which the FDA has granted Orphan Drug status and is being developed by Kyowa Hakko Kirin Pharma, and which is in a phase III trial for adult T cell leukemia (NCT01728805)
  • lirilumab is an anti-KIR antibody being developed by Bristol-Myers Squibb and is in a phase II trial for acute myeloid leukemia (NCT01687387)
  • CT-011, an anti-PD-1 antibody, and a dendritic cell vaccine are being tested in acute myelogenous leukemia in a phase II trial (NCT01096602)

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.

Updated July 2014

Sources: American Cancer Society Cancer Facts & Figures 2014; 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:

Holbrook Kohrt
Holbrook Kohrt, Ph.D.
Stanford Cancer Institute, Stanford, CA

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