osed with ALL achieve remission, a significant number of them relapse. Once they relapse, the prognosis is poor, with ALL accounting for the most number of deaths from cancer in children.
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 demonstrated to be an effective target using this approach. Therapies targeting CD19 in pediatric leukemia can be quite potent, and destroy both malignant and healthy B cells. B cells are a type of white blood cell that comprises the immune system. While loss of healthy B cells is not desirable, standard medical practice allows patients to tolerate this side effect without substantial toxicity.
The process of using genetically engineered T cells (another immune system cell) to recognize CD19 has already been demonstrated to be effective in adults with B cell malignancies, but studies in children are only now underway. In April 2013 at the annual meeting of the American Association for Cancer Research, Daniel W. Lee, M.D., assistant clinical investigator in NCI’s Pediatric Oncology Branch, and recipient of a fellowship from the non-profit St. Baldrick’s Foundation, discussed results from his ongoing clinical trial. This trial demonstrates anti-leukemia effects using lymphocytes engineered to target CD19 in cases of pediatric ALL that are refractory, or resistant to treatment.
Lee’s specific approach involves collecting T cells from children, modifying them in the laboratory so that they would attach to CD19 that is expressed by the leukemia cells. The number of modified T cells, called anti-CD19 CAR T cells, was increased nearly 60-fold in the laboratory before they were returned to the patients.
The researchers used this approach in patients whose disease was non-responsive or has returned after standard treatments. Thus far, the approach appears to be similarly tolerable and effective whether or not a person has had a bone marrow transplant, which many children with refractory ALL have previously undergone. This approach differs from one that, until fairly recently, has often been taken in adults, whereby the harvesting and expansion (increase in numbers) of the cells can take months. Pediatric patients are often in the terminal stages of their disease and don’t have months to wait. Therefore, Lee and his associates have developed a method that harvests and expands the cells in 11 days. This time differential turns out to be critical and life-saving.
The NCI Pediatric Oncology Branch’s outstanding advances in immunotherapy and other fields received special recognition at the 2013 AACR annual meeting via their selection to co-Lead a Stand Up 2 Cancer Pediatric Dream Team directed at “Immunogenomics to Create New Therapies for High-Risk Childhood Cancers.” Their participation in this highly competitive arena illustrates the high esteem the pediatric oncology community has for NCI research in this challenging area, per a statement from AACR: “The pediatric oncology research field will continue to benefit from the dedication of expert researchers such as you and your colleagues.”
Whatever the next step in immunotherapies for children may be, either in NCI’s Pediatric Oncology Branch or by other researchers across the country, it’s clear that recent clinical advances have real promise and will be integrated into many treatment modalities in the years to come. Significantly, they also have the potential to inform clinicians of how to better treat adult cancers.