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Rescuing T-Cell Function for Immunotherapy of Pediatric Malignancies

David M. Barrett, MD, PhD

Dr. Barrett is an assistant professor in the Department of Blood and Marrow Transplant at Children’s Hospital of Philadelphia. His SU2C Innovative Research Grant project, awarded in 2017, is titled, “Rescuing T-Cell Function for Immunotherapy of Pediatric Malignancies. “

CAR T-cell therapy is very effective in pediatric leukemia and has yielded remission rates of more than 90 percent for children with relapsed acute lymphoblastic leukemia (ALL) in early stage clinical trials. However, there remain a significant number of patients eligible for this treatment for whom a CAR T product cannot be made. Dr. Barrett, through his experience with the pediatric CAR T-cell program at Children’s Hospital of Philadelphia, has discovered that the main reason for this is the poor function of T cells from the patient—they are either defective or dead. Initial studies in the Barrett lab have shown that T cells from these patients have altered metabolic states. These metabolic alterations can be induced by chemotherapy but may also exist as part of the influence of particular types of cancer. Dr. Barrett seeks to identify the specific nature of these metabolic alterations in order to devise ways to reverse them, hence eventually enabling effective CAR T cells to be made. Additionally, the effect of chemotherapy on the metabolic status of T cells will be investigated in order to define therapeutic interventions to maintain T-cell efficacy for immunotherapy in the face of chemotherapy. This innovative approach to understanding how to enhance CAR T-cell production should shed urgently needed light on the process of CAR T-cell generation.