Vinodh Pillai, MD, PhD, CLIP Investigator Children's Hospital of Philadelphia Area of Research: Childhood Cancer, Leukemia, Lymphoma CAR T cell immunotherapies that use—and enhance—patients’ own T cells have provided remarkable benefits for patients with B cell leukemia that is resistant to chemotherapy. While this novel treatment is lifesaving in many children with B cell leukemia, some children do not respond or they respond early on but the leukemia returns within a few months. This is partially because not all cancers express CD19— marker that CAR T cells use to target leukemia cells—at the right level. Additionally, some leukemias can evolve to no longer express the CD19 marker at all in order to escape CAR T cells. Therefore, in order to improve the long-term benefits of CAR T cells for children with B cell leukemia, Dr. Vinodh Pillai aims to identify some of the important factors that determine who will respond to this therapy. Using clinical and experimental data, Dr. Pillai will test his hypothesis that cells with low levels of CD19 are resistant to killing by the CAR T cells, which are only activated by a certain level of CD19. Dr. Pillai will also determine why some children tend to lose the CD19 more than the others. Overall, this information should help improve our understanding of the mechanisms of CAR T cell activity and lead to the development of improved CAR T cell strategies for leukemia and other cancer types. Projects and Grants Predicting response to CAR T-cell Therapy Children’s Hospital of Philadelphia | Childhood Cancer, Leukemia, Lymphoma | 2020