Immunotherapy
For Leukemia Cancer

What Makes Immunotherapy for Leukemia a Promising Treatment?

Reviewed by:

Alex Huang, MD
Case Western Reserve University School of Medicine and Rainbow Babies & Children’s Hospital

Immunotherapy for leukemia provides several treatment options, and ongoing research demonstrates even greater potential for new treatments, especially in adoptive cell therapy.

Leukemia is cancer of the bone marrow and lymphatic system, and affects both children and adults. In leukemia, abnormal cells, produced by the bone marrow, begin to overtake and replace the normal blood and marrow cells.

There are four main types of leukemia, each named for the rate at which the disease develops and worsens as well as the affected blood cell type.

• acute myeloid leukemia (AML): fast-growing cancer that starts in myeloid cells—the precursor to red blood cells, platelets (cells that clot the blood), or white blood cells known as granulocytes; also known as acute myelogenous or myeloblastic leukemia
• chronic myeloid leukemia (CML): slower-growing cancer that starts in myeloid cells—the precursor to red blood cells, platelets (cells that clot the blood), or white blood cells known as granulocytes; also known as chronic myelogenous or myeloblastic leukemia
• acute lymphocytic leukemia (ALL): fast-growing cancer that starts in lymphoid cells, which make different types of white blood cells; also known as acute lymphoblastic leukemia
• chronic lymphocytic leukemia (CLL): slower-growing cancer that starts in lymphoid cells, which make different types of white blood cells; also known as chronic lymphoblastic leukemia

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.

Globally, an estimated 440,000 new cases of leukemia are diagnosed each year along with 310,000 deaths. There will be an estimated 60,000 new cases of leukemia in the United States in 2023, and more than 24,000 related deaths. Survival rates vary substantially by leukemia subtype, ranging from a current five-year relative survival rate of 27% for adults diagnosed with AML to 86% for those with CLL, and 66% for children, adolescents, and young adults diagnosed with AML to 92% for those with ALL. In 2018, there are an estimated 381,774 people living with or in remission from leukemia in the United States.

Leukemia Cancer Treatment Options

Treatment for leukemia depends on an individual’s age, cancer type, and the severity of the disease. In most cases, chemotherapy is the first line of treatment for this disease, though some patients require a stem cell transplant to eliminate the leukemia entirely.

Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. In addition to stem cell transplants, there are currently ten FDA-approved immunotherapy options for leukemia.

Targeted Antibodies

• Alemtuzumab (Campath®): a monoclonal antibody that targets the CD52 pathway; approved for subsets of patients with chronic lymphocytic leukemia (CLL)
• Blinatumomab (Blincyto®): a bispecific antibody that targets CD19 on tumor cells as well as CD3 on T cells; approved for subsets of patients with acute lymphoblastic leukemia (ALL)
• Gemtuzumab ozogamicin (MyloTarg®): an antibody-drug conjugate that targets the CD33 pathway and delivers toxic drugs to cancer cells; approved for subsets of adult and pediatric patients with CD33-positive acute lymphoblastic leukemia (ALL)
• Inotuzumab ozogamicin (Besponsa®): an antibody-drug conjugate that targets the CD22 pathway and delivers toxic drugs to cancer cells; approved for subsets of patients with advanced acute lymphoblastic leukemia (ALL)
• Obinutuzumab (Gazyva®): a monoclonal antibody that targets the CD20 pathway; approved for subsets of patients with CD20-positive chronic lymphocytic leukemia (CLL), including as a first-line therapy
• Ofatumumab (Arzerra®): a monoclonal antibody that targets the CD20 pathway; approved for subsets of patients with CD20-positive chronic lymphocytic leukemia (CLL), including as a first-line therapy
• Rituximab (Rituxan®): a monoclonal antibody that targets the CD20 pathway; approved for subsets of patients with chronic lymphocytic leukemia (CLL), including as a first-line therapy

Adoptive Cell Therapy

• Brexucabtagene autoleucel (Tecartus™): a CD19-targeting CAR T cell immunotherapy; approved for subsets of patients with acute lymphoblastic leukemia (ALL)
• Tisagenlecleucel (Kymriah®): a CD19-targeting CAR T cell immunotherapy; approved for subsets of children and young adult patients with acute lymphoblastic leukemia (ALL)

Immunomodulators

• Interferon alfa-2a (Roferin®-A): a cytokine that targets the IFNAR1/2 pathway; approved for subsets of patients with hairy cell leukemia and Philadelphia chromosome positive chronic myeloid leukemia (CML)
• Interferon alfa-2b (Intron A®): a cytokine that targets the IFNAR1/2 pathway; approved for subsets of patients with hairy cell leukemia and aggressive follicular non-Hodgkin lymphoma

New immunotherapies are currently being tested in leukemia clinical trials.

CRI’s Impact in Leukemia Cancer

Throughout our history, the Cancer Research Institute has funded numerous studies and clinical trials involving the treatment of leukemia with immunotherapy. Some of these studies have led to discoveries that have the potential to cure several subtypes of leukemia.

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, or Mylotarg), was developed by Irving Bernstein, MD, a CRI postdoctoral fellow from 1972-1974, and was approved by the FDA in 2000.
• Paola Betancur, PhD, a CRI postdoctoral fellow from 2014-2016 in the laboratory of Irving L. Weissman, MD, at Stanford University School of Medicine, is working to validate and test therapeutic strategies targeting the CD47 protein a “don’t eat me” signal that stops macrophages, a type of immune cell that engulfs and destroys its targets) to treat cancer.
• Kristen E. Pauken, PhD, a CRI postdoctoral fellow at the University of Pennsylvania from 2013-2016, along with Michael A. Farrar, PhD, a former CRI postdoctoral fellow and investigator award recipient at the University of Minnesota, found BCR-ABL leukemia actively suppresses immune responses by converting leukemia-specific T cells into inhibitory, regulatory T cells, aiding leukemia’s progression.
• CRI investigator Hiroyoshi Nishikawa, MD, PhD, at Osaka University found that several cancer-testis antigens, including NY-ESO-1, were highly expressed in adult T cell leukemia/lymphoma (ATLL) and that they could be recognized by killer T cells, providing proof-of-principle that cancer-testis antigens are a promising target for ATLL immunotherapy.
• CRI investigator Ryan Teague, PhD, at Saint Louis University School of Medicine has shown that blockade of CTLA-4, PD-1, and LAG-3 could restore anti-tumor activity in adoptively transferred T cells and result in durable and more effective anti-tumor immunity in advanced leukemia.

Explore CRI’s current funding for leukemia research in our funding directory.