Immunotherapy for Leukemia
Let's spread the word about Immunotherapy! Click to share this page with your community.
Copy Link
  • Science of Immunotherapy
  • Clinical Trials
  • CRI's Impact
  • Related News & Resources

How is Immunotherapy Changing the Outlook for Patients with Leukemia?

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

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 both children and adults with leukemia.

Featured Scientist
Nisarg J. Shah, Ph.D.
Harvard Medical School
Postdoctoral Fellow  |  2017
View Funding Directory
Leukemia Statistics
Main types of leukemia
>55 Years
Age most commonly affected by leukemia
Most common cancer in children <15 years old
Types of immunotherapy clinical trials
Urgent Need

Leukemia is a cancer of the blood and bone marrow, the soft material in the center of most bones. Leukemias are named for how quickly the disease develops and gets worse. Acute leukemia is a fast-growing cancer that usually gets worse quickly. Chronic leukemia is a slower-growing cancer that gets worse gradually over time. Leukemia is also named for the type of blood cell that is affected. Leukemia that starts in myeloid cells—the pathway that leads to red blood cells, platelets (cells that clot the blood), or white blood cells known as granulocytes—is called myeloid (or myelogenous/myeloblastic) leukemia. Leukemia that starts in lymphoid cells—which make different types of white blood cells—is called lymphocytic or lymphoblastic leukemia.

There are four main types of leukemia:

  • Acute myeloid leukemia (AML)
  • Acute lymphocytic leukemia (ALL)
  • Chronic myeloid leukemia (CML)
  • Chronic lymphocytic leukemia (CLL)

Leukemia occurs most often in adults older than 55 years, but it is the most common cancer in children younger than 15 years. Among adults, the most common types are CLL (35%) and AML (32%). Among children and teens, ALL is the most common, accounting for 75% of pediatric leukemia cases.

In the U.S., over 60,140 new cases of leukemia are expected in 2016, and more than 24,400 deaths will occur. Survival rates vary substantially by leukemia subtype, ranging from a current 5-year relative survival rate of 26.6% for patients diagnosed with AML, to 82.6% for those with CLL. In 2013, there were an estimated 333,975 people living with leukemia in the United States.


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 bispecific T cell engager (BiTE), consisting 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 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, Blincyto is also being tested in patients with Philadelphia chromosome-positive ALL, where it has also shown promise.

Gemtuzumab ozogamacin (MylotargTM), an anti-CD33 antibody-drug conjugate, is approved for CD33-positive acute myeloid leukemia (AML) in both adults and children who have relapsed as well as in newly diagnosed adults, while the combination of rituximab, an anti-CD20 targeted antibody, and hyaluronidase (Rituxan HycelaTM) has been approved for chronic lymphocytic leukemia (CLL). Most recently, tisagenlecleucel—a CAR T cell immunotherapy targeting the CD19 protein—was approved for children and young adults with ALL.

For those patients who relapse, or are not cured by existing approaches, newer treatments are badly needed.

Clinical Trials 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, checkpoint inhibitors, therapeutic vaccines, adjuvant immunotherapies, and cytokines.

  • Adoptive Cell Therapy
  • Monoclonal Antibodies
  • Checkpoint Inhibitors
  • Therapeutic Vaccines
  • Adjuvant Immunotherapies
  • Cytokines

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 (NCT02640209) and adult patients with ALL (NCT02030847).
  • City of Hope Medical Center is enrolling adult patients with ALL (NCT02146924) and AML (NCT02159495).
  • Fred Hutchinson Cancer Research Center is enrolling adult patients with ALL or CLL (NCT01865617).
  • Seattle Children’s Hospital is enrolling pediatric patients with CD19-positive leukemia (NCT02028455).
  • National Institutes of Health Clinical Center is enrolling adult patients with B cell leukemia (NCT02659943).
  • Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute are enrolling pediatric and young adult patients with relapsed ALL (NCT01430390).
  • Memorial Sloan Kettering Cancer Center is enrolling adult patients with CLL (NCT00466531) and adult patients with ALL (NCT01044069).
  • Baylor College of Medicine is enrolling both adult and pediatric patients with CLL and ALL (NCT01853631NCT02050347).
  • University College London is enrolling pediatric and young adult patients with ALL (NCT02443831NCT02808442).
  • Children’s Hospital of Philadelphia is enrolling pediatric and young adult patients with ALL (NCT02650414).
  • UC San Diego and Moffitt Cancer Center are enrolling adult patients with ALL (NCT02614066).
  • City of Hope, Children’s Hospital Los Angeles, Children’s Hospital of Orange County, and Children’s Hospital Colorado are enrolling pediatric and adolescents with ALL (NCT02625480).
  • The University of Texas MD Anderson Cancer Center is enrolling adult and pediatric patients with ALL or CLL (NCT02529813).

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 being tested in clinical trials: 

  • A phase III trial of vadastuximab talirine, a CD33 antibody-drug conjugate, in adult patients with newly diagnosed AML (NCT02785900).
  • A phase II trial of BI 836858, a CD33 antibody, in adult patients with AML (NCT02632721).
  • A phase II trial of MOR208, a CD19 antibody, in adult patients with CLL (NCT02639910) (not yet enrolling).
  • A phase I trial of IMGN779, a CD33 antibody-drug conjugate, in adult patients with CD33-positive AML (NCT02674763).
  • A phase I trial of lenzilumab, a CSF2 antibody, in adult patients with CML (NCT02546284).
  • A phase I trial of BI 836826, a CD37 antibody, in adult patients with CLL (NCT02759016).
  • A phase I trial of BTCT4465A, a bispecific antibody targeting CD20 and CD3, in adult patients with CLL (NCT02500407).
  • A phase I trial of ADCT-301, a CD25 antibody-drug conjugate, in adult patients with CD25-positive AML or ALL (NCT02588092).
  • A phase I trial of AGS67E, a CD37 antibody-drug conjugate, in adult patients with AML (NCT02610062).
  • A phase I trial of XmAb14045, a CD123 x CD3 antibody, in adult patients with AML, ALL, CML, or hairy cell leukemia (NCT02730312) (not yet enrolling).

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.

Nivolumab (Opdivo®): A PD-1 Antibody
  • A phase II trial, in combination with ipilimumab, a checkpoint inhibitor targeting CTLA-4, for adult patients with myelodysplastic syndrome (NCT02530463).
  • A phase II trial, in combination with lirilumab, an anti-KIR antibody, for adult patients with myelodysplastic syndrome (NCT02599649).
  • A phase II trial for adult patients with AML at high-risk for relapse (NCT02532231).
  • A phase II study for patients with AML to eliminate residual disease and maintain remission after chemotherapy (NCT02275533).
  • A phase II trial for relapsed, refractory or high-risk untreated patients with CLL, with ibrutinib (NCT02420912).
  • A phase II trial for adult patients with human T cell leukemia virus (HTLV)-associated leukemia (NCT02631746).
  • A phase I trial for adult patients with chromosome-positive ALL, with dasatinib, an oral kinase inhibitor (NCT02819804).
Pembrolizumab (Keytruda®, MK-3475): A PD-1 Antibody
  • A phase II trial in adult patients with minimal residual disease in ALL (NCT02767934).
  • A phase II trial in adult patients with AML (NCT02845297).
  • A phase II trial in adult patients with relapsed or refractory AML (NCT02768792).
  • A phase II trial to reduce relapse in AML in adult patients who are not eligible for transplant (NCT02771197).
  • A phase II trial in adult patients ≥60 with AML, post-remission (NCT02708641).
  • A phase II study in patients with relapsed or refractory CLL (NCT02332980).
  • A phase I/II trial, in combination with ublituximab, targeting CD20, and TGR-1202, a PI3K delta inhibitor, in adult patients with relapsed or refractory CLL (NCT02535286).
Durvalumab (MEDI4736): A PD-L1 Antibody
  • A phase II trial in previously untreated adult patients with myelodysplastic syndrome or elderly patients with AML (NCT02775903).
  • A phase I/II trial in adult patients with CLL (NCT02733042).
Atezolizumab (Tecentriq™, MPDL3280A): A PD-L1 Antibody
  • A phase II trial, in combination with obinutuzumab and ibrutinib, in adult patients with relapsed, refractory, or high-risk untreated CLL (NCT02846623).
CD47 Antibodies
  • A phase I trial of Hu5F9-G4 in adult patients with myeloid and monocytic leukemia (NCT02678338).
  • A phase I trial of CC-90002 in adult patients with AML or high-risk myelodysplastic syndrome (NCT02641002).
  • A phase I trial of REGN2810, a PD-1 antibody, and REGN1979, in anti-CD20/CD3 antibody, in adult patients with ALL (NCT02651662).
  • A phase I trial of BGB-A317, a PD-1 antibody, and BGB-3111, a BTK inhibitor, in adult patients with B cell cancers (NCT02795182).
  • A phase II trial of lirilumab, an anti-KIR antibody, combined with rituximab for relapsed, refractory or high-risk untreated patients with CLL (NCT02481297).
  • A phase I/II trial of monalizumab (IPH2201), an anti-NKG2A antibody, in adult patients with relapsed or refractory CLL (NCT02557516).


Therapeutic vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Vaccines in clinical testing include:

  • A phase II trial of patient-individualized peptide vaccine, in combination with lenalidomide, in adult patients after first-line therapy for CLL (NCT02802943).
  • A phase I/II trial of a dendritic cell vaccine for adult patients with CML (NCT02543749).
  • A phase I trial of tumor-associated antigen-specific T cells, targeting the WT1, NY-ESO-1, PRAME, and survivin markers, which are expressed on most AML and MDS cancer cells, in adult patients (NCT02494167).
  • A phase I trial of DSP-7888, a WT1 protein-derived peptide vaccine, in adult patients with advanced cancers, including AML and MDS (NCT02498665).

Adjuvants are substances that are either used alone or combined with other immunotherapies to boost the immune response.

  • A phase I/II trial of an IDO inhibitor, indoximod, with chemotherapy for adult patients with newly diagnosed AML (NCT02835729). IDO is expressed by cancer cells in a range of tumor types, and high IDO expression appears to correlate with poor outcomes in a number of cancers.

Cytokines are messenger molecules that help control the growth and activity of immune system cells.

  • A phase I trial of IL-15 and alemtuzumab in adult patients with relapsed or refractory T cell leukemia (NCT02689453).

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 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 ado-trastuzumab  from Genentech, which was approved by the FDA in 2013 for breast cancer, and brentuximab vedotin, an ADC to CD30, approved by the FDA in 2011 for Hodgkin’s lymphoma, from Seattle Genetics.
  • 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.
  • Patients with the fusion gene BCR-ABL, also called the Philadelphia chromosome, develop chronic myelogenous leukemia (CML). Kristen E. Pauken, Ph.D., a CRI postdoctoral fellow at the University of Pennsylvania, Philadelphia, PA, along with Michael A. Farrar, Ph.D., a former CRI postdoctoral fellow and investigator award recipient at the University of Minnesota, were wondering whether the fusion of BCR to ABL generates a potential leukemia-specific antigen that could be a target for immunotherapy. They found, however, that BCR-ABL-specific T cells converted into regulatory T cells—a class of cells that exert a dominant regulation on other immune cells. Thus, BCR-ABL leukemia actively suppresses immune responses by converting leukemia-specific T cells into inhibitory, regulatory T cells, aiding leukemia’s progression. These finding were reported in the Journal of Immunology.
  • 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 costimulatory 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.
  • 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 July 2016

Sources: American Cancer Society Cancer Facts & Figures 2016; GLOBOCAN 2012; SEER Cancer Statistics Factsheets: Leukemia (National Cancer Institute); What You Need To Know About™ Leukemia (National Cancer Institute);; 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)

*Immunotherapy results may vary from patient to patient.