局部区域给药增强抗 GPC3 CAR-T 细胞抗肝细胞癌功能

In this study, we constructed anti-GPC3 CAR-T cells and examined their therapeutic efficacy through locoregional and systemic administration using multiple HCC xenograft mouse models.

Comparison of CAR-T cell injections via portal vein and tail vein in mice with orthotopic HepG2 tumours demonstrated significantly enhanced tumour growth inhibition with locoregional CAR-T therapy. Consistently, tumour infiltration of CAR-T cells was significantly enhanced by portal vein injection and correlated with increased cytotoxicity, enhanced chemotaxis and reduced exhaustion of the tumour-infiltrating CAR-T cells compared to the tail vein injection group. Treatment with escalating CAR-T cell dosages resulted in further improved functionality of CAR-T cells and treatment efficacy, alongside improved liver function. Furthermore, portal vein injection exhibited superior tumour inhibition compared to tail vein injection in a metastatic model concurrently bearing orthotopic and extrahepatic tumour lesions.

Collectively, our study demonstrates that locoregional CAR-T therapy through the portal vein is associated with increased CAR-T cell infiltration and improved therapeutic efficacy, offering promise for the treatment of both early- and late-stage patients.