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The persistent clinical failure has driven interest in novel, immune-based strategies with higher specificity and greater cytotoxic potency, among which chimeric antigen receptor (CAR)-T-cell therapy has emerged as a leading approach. \u03b1\u03b2 CAR-T cells demonstrate safety but limited efficacy due to antigen heterogeneity, an immunosuppressive tumor microenvironment (TME), and restricted trafficking to the central nervous system (CNS). \u03b3\u03b4 CAR-T cells, combining innate major histocompatibility complex (MHC)-independent tumor recognition with engineered antigen specificity, have demonstrated preclinical cytotoxicity and features consistent with intratumoral persistence in selected models, as well as off-the-shelf potential, making them a next-generation immunotherapy strategy for 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