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For CAR-T cell therapy to succeed in GBM, several challenges must be overcome, including the immunosuppressive microenvironment (immunosuppressive cells, hypoxia, and metabolic constraints), antigen heterogeneity, and the anatomically isolated environment. To address these challenges, next-generation CAR-T cells\u2014those engineered with additional functionalities\u2014have been developed, and phase 1 clinical trials evaluating these next-generation CAR-T therapies for GBM have now been initiated. The development of CAR-T therapy for GBM has entered a new chapter. 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