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NCI Reviews Cancer Immunotherapy in Children and Adults

Little change in cancer survival rates since 2000 (Apr. 8)

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 aged 14 years and younger compared with more 1.6 million cases diagnosed in adults.

According to Crystal L. Mackall, MD, chief of the Pediatric Oncology Branch of the National Cancer Institute (NCI), “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% of children diagnosed with cancer are cured. Still, cancer remains the leading cause of disease-related death in children over 1 year of age, and the late effects of standard therapies for childhood cancer are substantial.” Moreover, the outcomes for high-risk pediatric patients (those diagnosed at advanced stages of their diseases) remain quite poor.

Mackall notes that significant progress was made in treating childhood cancers from the 1960s until about 2000, but there has been a plateau in childhood cancer survival rates during the past decade, particularly for 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%, according to the NCI.

To address these challenges, researchers have been developing new immunotherapies, either administered alone or in combination with standard chemotherapy, radiation therapy, and/or surgery. One approach that has been studied extensively is the use of cancer vaccines, the NCI says. In 2010, the FDA approved the first vaccine for any type of cancer — sipuleucel-T (Provenge, Dendreon) for the treatment of prostate cancer. Investigators are looking at whether tumor vaccines administered as pre-emptive or adjuvant therapies may be beneficial in more aggressive cancers.

One type of adjuvant therapy is dendritic cell vaccination, which has been studied in the NCI’s Pediatric Oncology Branch for children with high-risk pediatric sarcomas. According to the NCI, this therapy has shown dramatic effects on immune reconstitution with higher CD4 counts, and early results suggest improved long-term control of the cancer.

Another, more aggressive immunotherapy for 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 into 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 the National Institutes of Health (NIH).

Beyond cell-transfer techniques, genetic engineering can be used to reprogram the patient’s lymphocytes to recognize and kill any cell that carries a specific target protein on its surface. For pediatric ALL, the CD19 protein has been shown to be an effective target using this approach. However, therapies targeting CD19 in pediatric leukemia can destroy both malignant and healthy B cells.

The NCI notes that, whatever the next step in immunotherapies for children may be, recent clinical advances have shown promise and will be integrated into numerous treatment modalities in the years to come. Significantly, they also have the potential to inform clinicians of how to better treat adult cancers.

Source: NCI; April 8, 2013.

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