Systematic analysis of locoregional delivery of CAR T cells in high-grade gliomas

Use of CAR-T therapy in high-grade gliomas (HGG) is challenged by the blood-brain barrier, limited efficacy, and significant toxicities associated with systemic administration. Systematic review of published studies evaluated the safety and efficacy of locoregional (intracerebroventricular) versus systemic CAR-T cell delivery for HGG. The analysis included 14 clinical trials with 194 patients. Locoregional delivery compared with systemic delivery was associated with a markedly improved safety profile and antitumor activity, demonstrating an over 60% reduction in the incidence of grade ≥ 3 adverse events (RR 0.39; p<0.001) and rates of disease responses not widely observed with systemic approaches (RR 3.79; pxtagstartz0.05). Locoregional delivery also enables the analysis of cerebrospinal fluid to monitor T-cell trafficking and emerging biomarkers of immune activitation. The authors conclude that these findings support intracranial delivery of CAR-T cells in HGG.