CAR-T cells immunotherapy in the treatment of glioblastoma.

Glioblastoma multiforme (GBM) is highly lethal brain tumor with limited benefit from standard treatment, such as surgery, radiotherapy, and chemotherapy. Its location within the central nervous system, together with the blood-brain barrier, and immunosuppressive niche restricts access and efficacy of therapies. This review examines the current progress of the chimeric antigen receptor (CAR) T cell therapy in GBM, emphasizing therapeutically significant target antigens, delivery strategy and innovations designed to improve safety and persistence. Evidence from preclinical research and early phase clinical trials was assessed to identify key antigen, evaluate routes of administration, and summarize next-generation engineering concepts. Clinical experiences demonstrate that locoregional delivery can enhance tumor penetration compared with systemic infusion. Moreover, CAR-T cells engineered to recognize epidermal growth factor receptor variant III, interleukin-13 receptor subunit alpha-2, human epidermal growth factor receptor 2, or disialoganglioside have shown biological activity in GBM. Emerging platforms, such as dual-target CARs, synNotch, and cytokine-releasing "armored" T cells, develop specificity and overcome barriers posed by tumor heterogeneity and immune suppression. CAR-T therapy in GBM has moved beyond proof-of-concept, with encouraging but preliminary signals of efficacy. Future success will require multi-target approaches, integration with modulators of tumor microenvironment, and optimized delivery systems to achieve durable clinical benefit.