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Immunotherapy for Childhood Cancer

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  • Childhood Cancer
  • Treatment Options
  • CRI's Impact
  • Clinical Trials

How is Immunotherapy Changing the Outlook for Children with Cancer?

Reviewed By: Alex Huang, M.D.
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Around the world, young people under the age of 20 receive a cancer diagnosis roughly every two minutes, affecting an estimated 300,000 children and adolescents every year. Although young people are affected by several of the same types of cancer as adults, the ways in which they develop―and the ways in which they must be treated―can be drastically different for several reasons.

Most cancers affecting young people involve a precursor cell, known as “blast” cells. Blast cells play a role in the formation of our bodily tissues, including our blood and immune cells, bones, eyes, and brains.

The most common types of cancer in children under the age of 15 are:

  • acute lymphocytic leukemia
  • brain cancer
  • neuroblastoma
  • non-Hodgkin lymphoma

The most common types of cancer in adolescents between the ages of 15-19 are:

  • brain cancer
  • Hodgkin lymphoma
  • thyroid carcinoma
  • testicular germ cell tumors

For people under the age of 20, cancer causes more deaths than any other disease in the United States, where only accidents are responsible for more deaths in this group. Approximately 1 of every 285 people in the United States will be diagnosed with cancer before the age of 20, and in about 80% of these cases, the cancer will have metastasized to other tissues by the time it is discovered. The average age of diagnosis is six years old.

The survival rates for these different types of cancers vary, but overall the majority of young people diagnosed with cancer are able to survive long-term thanks to advances in treatments, including immune-based therapies, over the past several decades.

Current treatments help most children and adolescents overcome cancer, but that survival often comes at a cost, as these treatments can cause long-term damage that can affect these patients for the rest of their lives. With new immunotherapy approaches, hope now exists that we can treat young patients not only more effectively, but also―due to the specificity of the immune system―in ways that prevent the damaging side effects that can accompany conventional treatments.

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Childhood Cancer Treatment Options

Surgery, radiation, and chemotherapy are all common treatment options for childhood cancers. While chemotherapy and radiation have improved the survival of children with cancer over the past few decades and are effective for about 80% of young patients, those treatments often cause damaging, long-term side effects. Stem cell transplants have already been helpful for young patients with neuroblastoma, leukemia, and lymphoma, and there are many efforts under way to improve this treatment approach.

There are currently four approved immunotherapy options for childhood cancer:

Targeted Antibodies

  • Dinutuximab (Unituxin®): a monoclonal antibody that targets the GD2 pathway; approved for subsets of pediatric patients with neuroblastoma

Immunomodulators

  • Ipilimumab (Yervoy®): a checkpoint inhibitor that targets the CTLA-4 pathway; approved for subsets of pediatric patients with advanced melanoma
  • Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1 pathway; approved for subsets of pediatric patients with classical Hodgkin lymphoma

Adoptive Cell Therapy

  • Tisagenlecleucel AKA CAR T 19 (KYMRIAH®): a CD19-targeting CAR T cell immunotherapy; approved for subsets of pediatric patients with advanced leukemia

There are several immunotherapies under evaluation in clinical trials.

Find a pediatric cancer clinical trial

CRI's Impact on Childhood Cancer

Several decades ago, less than one in every ten children diagnosed with cancer survived long term. Now, almost 80% survive. Stem cell transplants, a form of immunotherapy, have been critical to improving these childhood cancer survival rates. However, these transplants, as well as an immunotherapeutic antibody that is approved for pediatric neuroblastoma (a form of nerve cell tumor), are used in combination with chemotherapy, which can produce debilitating long-term side effects for these young patients, including graft versus host disease (GVHD).

To help address that problem, CRI invests in a diversity of projects which might improve treatment options. Some researchers are exploring ways to effectively perform transplants without the need for chemotherapy, while others are revealing new insights regarding the relationship between cancer and the immune system that could lead to entirely new approaches that improve outcomes and safety.

  • Carl H. June, M.D., of the University of Pennsylvania, has led clinical trials that have successfully treated young patients with CAR T cells, including Emily Whitehead, who overcame her leukemia and has been cancer-free for over four years now.
  • Three CRI postdoctoral fellows—Kevin C. Barry, Ph.D., at the University of California, San Francisco; Sofia L. Novais de Oliveira, Ph.D., at the University of Wisconsin-Madison; and Kevin M. Sullivan, M.D., at the University of Washington School of Medicine—and assistant professor of medicine Amy K. Kim, M.D., at Johns Hopkins University are exploring how immunotherapy could help against fibrolamellar hepatocellular carcinoma (FL-HCC), a rare form of liver cancer that primarily affects young people.
  • Mark P. Rubinstein, Ph.D., a CRI CLIP Investigator (2016-2018) at the Medical University of South Carolina, is working to improve the effectiveness of stem cell transplants, a common treatment for childhood cancers, by eliminating the need to wipe out a patient’s existing immune system prior to treatment.
  • Bradley Wayne Blaser, M.D., Ph.D., a CRI Irvington Postdoctoral Fellow (2014-2016) at the Dana-Farber Cancer Institute, identified the factors that promote successful engraftment of transplanted stem cells in animal models, which he will then attempt to translate into improved approaches for human patients.

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

Donate to children's cancer research

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Childhood Cancer Statistics

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Childhood Cancer Clinical Trial Targets

Discover the different proteins, pathways, and platforms that scientists and physicians are pursuing to develop new cancer treatments. Use this information to consider your clinical trial options.

Therapies
  • Targeted Antibodies
  • Cancer Vaccines
  • Adoptive Cell Therapy
  • Immunomodulators
  • Oncolytic Virus Therapy

Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers (known as antigens) on cancer cells, in order to disrupt cancerous activity, especially unrestrained growth. Antibody-drug conjugates (ADCs) are equipped with anti-cancer drugs that they can deliver to tumors. Bi-specific T cell-engaging antibodies (BiTEs) bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. Antibody targets under evaluation in childhood cancer clinical trials include:

  • CD19: a receptor found on the surface of almost all B cells that influences their growth, development, and activity; often expressed by leukemia, lymphoma, and myeloma cells
  • CD20: a receptor found on the surface of B cells during their development; often expressed by leukemia, lymphoma, and myeloma cells
  • CD22: a receptor found primarily on the surface of mature B cells; often expressed by leukemia and lymphoma cells
  • CD30: a receptor that is expressed on certain types of activated immune cells; often expressed by leukemia and lymphoma cells
  • CD33: a surface receptor found on several types of immune cells; often expressed by leukemia cells
  • CD38: an immune cell surface protein that plays roles in cell adhesion and signaling; often expressed by leukemia and myeloma cells
  • CD52: a protein found on the surface of mature immune cells as well as other cell types
  • CD56: a protein found on both neurons and natural killer immune cells
  • DLL/Notch: a pathway that can promote cell growth
  • EGFR: a pathway that controls cell growth and is often mutated in cancer
  • GD2: a pathway that controls cell growth, adhesion, and migration, and is often abnormally overexpressed in cancer cells
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
  • PDGFRα: a surface receptor that plays a role in stimulating cell division and growth
  • RANKL: a protein that plays a role in bone regeneration and modeling, and is often overexpressed in cancer

Cancer 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. Cancer vaccines can be made from a variety of components, including cells, proteins, DNA, viruses, bacteria, and small molecules. Cancer vaccine targets under evaluation in childhood cancer clinical trials include:

  • Cytomegalovirus (CMV)-related antigens: foreign viral proteins expressed by CMV-infected cancer cells
  • HER2: a pathway that controls cell growth; commonly overexpressed in cancer and associated with metastasis
  • MAGE antigens: the genes that produce these proteins are normally turned off in adult cells, but cancer cells often reactivate their expression
  • NY-ESO-1: a protein that’s normally produced only before birth but is often abnormally expressed in cancer
  • Personalized neoantigens: these abnormal proteins arise from mutations and are expressed exclusively by tumor cells
  • Survivin: a protein that can prevent cellular death and is overexpressed by a number of cancer cell types
  • WT1: a protein that is often mutated and abnormally expressed in patients with cancer, especially Wilms’ tumor (WT)

Adoptive cell therapy takes a patient’s own immune cells, expands or otherwise modifies them, and then reintroduces them to the patient, where they can seek out and eliminate cancer cells. In CAR T cell therapy, T cells are modified and equipped with chimeric antigen receptors (CARs) that enable superior anti-cancer activity. Natural killer cells (NKs) and tumor infiltrating lymphocytes (TILs) can also be enhanced and reinfused in patients. Cell-based immunotherapy targets under evaluation in childhood cancer clinical trials include:

  • CD19: a receptor found on the surface of almost all B cells that influences their growth, development, and activity; often expressed by leukemia, lymphoma, and myeloma cells
  • CD22: a receptor found primarily on the surface of mature B cells; often expressed by leukemia and lymphoma cells
  • CD30: a receptor that is expressed on certain types of activated immune cells; often expressed by leukemia and lymphoma cells
  • CD33: a surface receptor found on several types of immune cells; often expressed by leukemia cells
  • CD56: a protein found on both neurons and natural killer immune cells
  • CD123 (also known as IL-3R): a receptor found on immune cells that’s involved in proliferation and differentiation, and often expressed by leukemia and lymphoma cells
  • Epstein-Barr Virus (EBV)-related antigens: foreign viral proteins expressed by EBV-infected cancer cells
  • EGFR: a pathway that controls cell growth and is often mutated in cancer
  • GD2: a pathway that controls cell growth, adhesion, and migration, and is often abnormally overexpressed in cancer cells
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
  • NY-ESO-1: a protein that’s normally produced only before birth but is often abnormally expressed in cancer
  • Tumor-associated antigens (TAAs): proteins often expressed at abnormally high levels on tumor cells that can be used to target them; also found on normal cells at lower levels
  • WT1: a protein that is often mutated and abnormally expressed in patients with cancer, especially Wilms’ tumor (WT)

Immunomodulators manipulate the “brakes” and “gas pedals” of the immune system. Checkpoint inhibitors target molecules on immune cells to unleash new or enhance existing immune responses against cancer. Cytokines regulate immune cell maturation, growth, and responsiveness. Adjuvants can stimulate pathways to provide longer protection or produce more antibodies. Immunomodulator targets under evaluation in liver cancer clinical trials include:

  • CD40: activating this co-stimulatory pathway can kick-start adaptive immune responses
  • CTLA-4: blocking this pathway can help promote expansion and diversification of cancer-fighting T cells
  • CXCR4: blocking this pathway can promote the migration and recruitment of immune cells
  • IDO: blocking this enzyme’s activity can help prevent cancer-fighting T cells from being suppressed
  • IL-2/IL-2R: activating this cytokine pathway can help promote the growth and expansion of cancer-fighting T cells
  • LAG3: blocking this pathway may be able to help prevent suppression of cancer-fighting T cells
  • PD-1/PD-L1: blocking this pathway can help prevent cancer-fighting T cells from becoming “exhausted,” and can restore the activity of already-exhausted T cells
  • Toll-like receptors (TLRs): activation of these innate immune receptors can help stimulate vaccine-like responses against tumors

Oncolytic virus therapy uses modified viruses that can infect tumor cells and cause them to self-destruct. This can attract the attention of immune cells to eliminate the main tumor and potentially other tumors throughout the body. Viral platforms under evaluation in childhood cancer clinical trials include:

  • Herpes simplex virus: a virus that can cause the formation of sores on the mouth and genitals
  • Measles virus: a highly contagious virus that infects the respiratory tract and can cause measles
  • Reovirus: a family of viruses that can affect the gastrointestinal and respiratory tracts in a range of animal species
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Sources: National Cancer Institute, Cancer in Children and Adolescents Page; International Agency for Research on Cancer Report, 2016

Updated November 2018

*Immunotherapy results may vary from patient to patient. Consult a healthcare professional about your treatment options.

*Immunotherapy results may vary from patient to patient.

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