Over the past few years, outcomes and findings from several phase 1 clinical trials evaluating chimeric antigen receptor (CAR)-T cell therapies for glioblastoma (GBM) have been reported. 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—those engineered with additional functionalities—have 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. To date, the antitumor efficacy of CAR-T therapies still needs to be improved, and the high frequency of neurotoxicity remains a major issue that needs to be addressed; however, there is a growing anticipation that next-generation CAR-T therapies may provide clinical benefit to patients.
Yamaguchi et al. (2026) studied this question.