Abstract
BACKGROUND: This study aimed to investigate the safety and efficacy of fourth-generation combined PSMA and GD2-targeted chimeric antigen receptor (CAR)-T cells in the treatment of refractory/relapsed gliomas. METHOD: This study employed a single-arm design, enrolling patients with confirmed refractory/relapsed gliomas at the Immuno-oncology Department of the Cancer Center at Clifford Hospital in Guangdong. Eligible patients received combined treatment with PSMA CAR-T and GD2 CAR-T cells via intravenous administration. The dose of reinfused CAR-T cells ranged from 1-5 × 10^6 cells/kg of body weight. RESULTS: Six patients were included in the study, all of whom responded to the treatment. The overall response rate (ORR) was 50%, with three patients achieving complete response (CR) (50%) and three demonstrating stable disease (SD) (50%). The median progression-free survival (PFS) was 9.0 months (range, 1-56 months), and the median overall survival (OS) was 24.5 months (range, 13-63 months). Three patients (50%) developed cytokine release syndrome (CRS), all of which were classified as grade I CRS, and no patients experienced immune effector cell-associated neurotoxicity Syndrome (ICANS). CONCLUSION: Combined PSMA CAR-T and GD2 CAR-T cell therapy demonstrated significant efficacy and good tolerability in the treatment of refractory/relapsed gliomas, without severe adverse reactions.