Cancer immunotherapy in children: How does it differ from approaches in adults?
More often than not, cancer immunotherapies that work in adults are used in modified ways in children. Seldom are new therapies developed just for children, primarily because of the small number of pediatric patients relative to the adult cancer patient population. In 2013 there will be an estimated 11,630 cases of cancer diagnosed in children 14 and younger compared to over 1.6 million cases diagnosed in adults.
According to Crystal L. Mackall, M.D., chief of the National Cancer Institute’s Pediatric Oncology Branch, “Progress against childhood cancer represents one of the success stories of modern medicine. Pediatric cancers were uniformly fatal 60 years ago, but today more than 75 percent of children diagnosed with cancer are cured. Still, cancer remains the leading cause of disease-related death in children over one year of age, and the late effects of standard therapies for childhood cancer are substantial.” The outcomes for high-risk pediatric patients (those diagnosed at advanced stages of their diseases) remain quite poor.
Mackall notes that there was significant progress made in treating childhood cancers from the 1960s until about 2000, but there has been a plateau in childhood cancer survival rates for the past decade, particularly for those children with solid tumors such as Ewing sarcoma. Of particular concern is the cost to a patient’s longer term health due to late effects of therapy, such as another cancer arising due to the toxicity of the initial treatment. Two-thirds of survivors have late effects, with one-third having severe late effects, despite the fact that survival rates still hover around 75 percent.
To address these challenges, researchers have been developing new immunotherapies, either administered alone or used in combination with standard chemotherapy, radiation therapy and/or surgery. When discussing immunotherapy, one approach that has been studied extensively is the use of cancer vaccines. In 2010, the U.S. Food and Drug Administration approved the first vaccine for any type of cancer—Sipuleucel-T (trade named Provenge)—to treat prostate cancer. This treatment prolongs life in prostate cancer but does not induce tumor regression and thus may have less applicability for more aggressive, rapidly growing cancers, such as many childhood cancers. Therefore, many clinicians are looking at whether tumor vaccines administered as pre-emptive or adjuvant therapies (those that follow or are added onto the primary therapy), might be beneficial in more aggressive cancers. This model is particularly relevant to the field of childhood cancers, where remission is often achieved even in the most aggressive diseases.
One type of adjuvant therapy is dendritic cell vaccination, which has been studied in NCI’s Pediatric Oncology Branch for patients with high-risk pediatric sarcomas. For this therapy, patients travel to the National Institutes of Health (NCI is part of NIH) clinical center, where lymphocytes are collected, then the patients return home to their local clinics for chemotherapy or radiation, and finally return to NIH after completion of standard therapy for a combination of dendritic cell vaccination plus therapy for reconstitution of their immune system. This therapy has shown dramatic impact on immune reconstitution with higher CD4 (a type of white blood cell, or lymphocyte, that is important in fighting infection) counts and early results suggest improved long-term control of the cancer.
Another, more aggressive immunotherapy that has the capacity to treat established cancers, is adoptive cell transfer, a method in which lymphocytes are withdrawn from a patient, activated and/or modified in a culture to boost their tumor-fighting ability, and then re-infused in the patient. This approach has shown benefit in treating some patients with melanoma. The technique is now being applied to children with acute lymphoblastic leukemia (ALL) in clinical trials at NIH. Although more than 95 percent of children initially diagn