Immunotherapy:
For Childhood Cancer

How is Immunotherapy Changing the Outlook for Children with Cancer?

Reviewed by:

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

Immunotherapy for childhood cancer shows promise in certain cancers and without the damaging, long-term side effects that can accompany conventional treatments.

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. Approximately 1 of every 285 people in the United States will be diagnosed with cancer before the age of 20, and 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 may cause long-term damage that can affect these patients for the rest of their lives. With new immunotherapy approaches, hope now exists that young patients can be treated not only more effectively, but also―due to the specificity of the immune system―in ways that may prevent the damaging side effects that often accompany conventional treatments.

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.

Immunotherapy is a class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently five FDA-approved immunotherapy options for childhood cancer:

Targeted Antibodies

• Blinatumomab (Blincyto®): a bispecific antibody that targets CD19 on tumor cells as well as CD3 on T cells; approved for subsets of children with acute lymphoblastic leukemia (ALL)
• Dinutuximab (Unituxin®): a monoclonal antibody that targets the GD2 pathway; approved for subsets of pediatric patients with neuroblastoma
• Rituximab (Rituxan®): a monoclonal antibody that targets the CD20 pathway; approved for subsets of pediatric patients with certain leukemias and lymphomas

• 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

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.

CRI’s Impact on Childhood Cancer

Several decades ago, fewer 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 may 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, MD, 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 remains cancer-free.
• Three CRI postdoctoral fellows—Kevin C. Barry, PhD, at the University of California, San Francisco; Sofia L. Novais de Oliveira, PhD, at the University of Wisconsin-Madison; and Kevin M. Sullivan, MD, at the University of Washington School of Medicine—and assistant professor of medicine Amy K. Kim, MD, 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, PhD, 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, MD, PhD, 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.