Advances and challenges in CAR-T therapy for glioblastoma

Glioblastoma (GBM) remains one of the most lethal primary brain tumors, with current standard therapies conferring only limited survival benefit. Although immunotherapeutic approaches have expanded treatment options, they have yet to demonstrate consistent and durable efficacy. Chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising platform with the potential to overcome critical limitations of existing strategies. This review highlights the unique advantages of CAR-T therapy in complementing both standard and immune-based treatments. It further summarizes clinical outcomes reported to date, encompassing completed and ongoing trials, and underscores recurring barriers such as antigen heterogeneity, limited persistence, and the profoundly immunosuppressive tumor microenvironment. In view of these challenges, we discuss emerging strategies to advance CAR-T therapy in GBM, including approaches to broaden antigen recognition, enhance effector function, improve safety, and explore alternative cellular platforms. With continued innovation and rigorous clinical evaluation, CAR-T therapy holds considerable promise for delivering meaningful and durable benefit to patients with GBM.