Abstract
Chimeric antigen receptor (CAR) T cell therapy is a promising investigational modality for glioblastoma (GBM), but durable disease control has been limited by antigen heterogeneity, adaptive resistance, and an immunosuppressive tumor microenvironment. Early phase I studies targeting IL-13Rα2, HER2, EGFRvIII, EphA2, B7-H3, and GD2 established proof-of-concept for CAR T cell therapy in recurrent GBM and provided important clinical insights regarding feasibility, safety, and resistance mechanisms. More recent approaches, including multi-antigen targeting and locoregional delivery, aim to address these limitations, and ongoing trials evaluating new antigens and engineered platforms may further expand the clinical potential of CAR T cells in GBM.