Reappearance of Dawn: CAR-T Restricts Glioblastoma

Dear Colleagues,

Current exploration of CAR-T cell therapy for glioblastoma (GBM) demonstrates promising feasibility, safety, and preliminary efficacy, alongside dose tolerance and combinatorial potential with other immunotherapies. While dual/multivalent CAR-T cells are built upon single-target foundations, their efficacy is not necessarily superior. Despite theoretical advantages of multiplexed antigen targeting, challenges persist across multiple domains: mismatched antibody affinity, high production costs, potential neurotoxicity, treatment-related complications, and inconsistent clinical responses.

CAR-T therapy in GBM continues to face biological and technical barriers, including antigen escape, intratumoral heterogeneity, and an immunosuppressive tumor microenvironment that impairs cytotoxic function. Further limitations involve suboptimal tumor antigen expression, limited targetable tumor mass post-resection, and inefficient CAR-T cell trafficking across the blood-brain barrier. Although immune checkpoint blockade has shown benefits, its efficacy in GBM is restricted by limited T-cell infiltration. 

Therefore, larger patient cohorts and longer follow-up studies are required. Future research will focus on innovative strategies, such as low-intensity pulsed focused ultrasound, SynNotch CAR-T cells designed to open the blood–brain barrier, and MR-guided focused ultrasound.

Prof. Dr. Qianxue Chen
Guest Editor

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