FLASH radiation and NKG2D CAR T Cell therapy for glioblastoma treatment 4545

Abstract Description Glioblastoma Multiforme (GBM) is the leading cause of brain tumor-related deaths. Standard-of-care treatment involves surgery, chemotherapy, and radiotherapy (RT), resulting in a median overall survival of 17 months. More effective treatments are urgently needed. Ultra-high dose rate RT (FLASH-RT) preserves tumor control in murine GBM models compared to conventional RT (CONV-RT) while preserving normal healthy tissue. We found that RT induces higher expression of Rae-1, a stress ligand recognized by natural killer group 2D (NKG2D). Chimeric antigen receptor (CAR) T cells expressing a recombinant NKG2D CAR efficiently killed SB28 GBM tumor cells in vitro. We hypothesize that FLASH-RT can selectively sensitize GBM cells to NKG2D-CAR T cell immunotherapy while sparing normal brain tissue in vivo. To test our hypothesis, we first used spatial transcriptomics and detected transcriptional differences in orthotopic SB28 GBM tumors treated with FLASH-RT versus CONV-RT. We are currently evaluating the efficacy of FLASH-RT versus CONV-RT to synergize with NKG2D CAR T cells in both dermal and orthotopic SB28 models. The ability of FLASH-RT to sensitize GBM tumors to NKG2D-CAR T cell immunotherapy and enhance tumor cell killing may provide a much needed treatment for this deadly cancer. Funding Sources T32 AI007363 Topic Categories Neuroimmunology (NEUR)