2025 Volume 62 Issue 3 Pages 208-213
The chimeric antigen receptor (CAR) is an artificial receptor that employs single-chain antibodies or natural ligand/receptor binding as its specific antigen-binding sites. CAR T-cell therapies have demonstrated remarkable efficacy in clinical trials for relapsed and refractory hematological malignancies. In contrast, CAR T-cell therapy application for solid tumors lags significantly behind that for hematological malignancies. Key challenges include overcoming heterogeneous target antigen expression and the multiple immune escape mechanisms mediated by the tumor tissue microenvironment.
This article discusses the current clinical development in CAR T-cell therapy for brain tumors, which are unique because of the presence of a blood-brain barrier in comparison with extracranial solid tumors. Intraventricular or intratumoral administration via catheters is frequently used in clinical trials. Tumor inflammation-associated neurotoxicity (TIAN) is a reported complication. Clinical development has focused primarily on glioblastomas in adults and pediatric tumors, including diffuse intrinsic pontine gliomas, ependymomas, and other pediatric tumor types. Although some cases have shown neurological symptoms improvement and tumor shrinkage (radiographically confirmed), durable responses remain limited. Therefore, further research and improvements in target antigen selection, receptor structure, and T-cell function are needed.
