Federal Project Grant Award Summary

The National Cancer Institute awarded the University of Pennsylvania $618,063 under the Cancer Treatment Research program (CFDA 93.395) to develop FLASH-CAR-T radioimmunotherapy as an innovative treatment approach for pediatric brain tumors, including medulloblastoma and glioma. The five-year project, which commenced July 1, 2026 and concludes June 30, 2031, will deliver research and development services focused on combining FLASH (fast low-dose-rate radiotherapy) proton beam radiation with chimeric antigen receptor (CAR) T cell immunotherapy. The research will investigate how FLASH radiotherapy reprograms tumor-associated macrophages toward anti-tumor inflammatory phenotypes, enhances CAR T cell infiltration into tumors, and modulates lipid metabolism and tumor vasculature to overcome the immunosuppressive microenvironment that currently limits T cell-based therapies in pediatric brain malignancies.

The project will generate preclinical research products including mechanistic insights into neuroimmunological processes in brain tumors, translational data supporting the therapeutic efficacy of combined FLASH radiotherapy and CAR-T cell approaches, and foundational evidence to advance this therapeutic strategy toward clinical development. Deliverables will encompass laboratory studies utilizing genetically engineered mouse models, single-cell transcriptome analyses, in vivo T cell trafficking assays, and mechanistic investigations of immune cell reprogramming, with findings intended to establish FLASH-CAR-T radioimmunotherapy as a viable immunomodulatory approach for pediatric cancer treatment.