嵌合抗原受体T细胞免疫疗法在肝癌中的应用进展

Application Progress of Chimeric Antigen Receptor T-Cell Immunotherapy in Liver Cancer

嵌合抗原受体T细胞(CAR-T细胞)疗法已在肝癌治疗中表现出极大潜力。多种肿瘤相关抗原被用于肝癌的CAR-T细胞疗法,包括claudin18.2、癌胚抗原、甲胎蛋白等。但CAR-T细胞疗法仍存在一定的局限性,如难以到达肿瘤部位、肿瘤外效应、肿瘤的免疫抑制微环境、肿瘤对CAR-T细胞疗法的耐药性、肿瘤相关抗原异质性及不良反应。研究者已使用多种策略来应对CAR-T细胞疗法的局限性,以提高其有效性和安全性。虽然CAR-T细胞疗法在肝癌领域已表现良好的临床获益,但仍存在耐药和安全性等问题,开发新的肿瘤相关抗原、确定输注剂量、用药途径、适用人群和联用方案是未来的研究方向。

Chimeric antigen receptor T-cell(CAR-T cell)therapy has shown great potential in treating liver cancer.A variety of tumor-associated antigens have been used in CAR-T cell therapy for liver cancer,including claudin18.2,carcinoembryonic antigen,α-fetoprotein,etc.However,there are still limitations of CAR-T cell therapy in the treatment of solid tumors such as liver cancer,such as the difficulty of CAR-T cell to reach the tumor site,off-tumor effects,immunosuppressive microenvironment of tumors,tumor resistance to CAR-T cell therapy,heterogeneity of tumor-associated antigens,and adverse effects of CAR-T cell therapy.Researchers have used various strategies to address these limitations of CAR-T cell therapy to improve its efficacy and safety.Although CAR-T cell therapy has achieved remarkable clinical efficacy in the treatment of liver cancer,there are still issues with drug resistance and safety.Development of new tumor-associated antigens,determination of infusion doses,routes of administration,applicable populations and combination regimens are directions for the further research.