嵌合抗原受体T细胞治疗原发性肝癌临床研究进展

Clinical research advances in chimeric antigen receptor T-cell therapy for primary liver cancer

原发性肝癌具有起病隐匿以及早期诊断困难等特点,治疗手段有限且效果不佳。嵌合抗原受体(CAR)T细胞疗法是经基因编辑修饰的T淋巴细胞识别肿瘤特异性抗原并活化T淋巴细胞,发挥肿瘤杀伤作用。CAR-T细胞疗法治疗血液肿瘤取得重大进展,近年来在实体瘤领域也有了很好的临床疗效,尽管CAR-T细胞治疗技术已经从第一代发展到第五代,但在实体瘤领域仍存在诸多挑战。本文将对CAR-T细胞治疗原发性肝癌的机制以及相关研究进展进行全面的综述,包括目前CAR-T细胞疗法治疗原发性肝癌主要的靶点GPC3、AFP、MUC1、NKG2D等,CAR-T细胞治疗与溶瘤病毒,逐渐兴起的免疫检查点抑制剂等联合治疗,以及对以上靶点以及治疗方式的生物学研究、临床前研究和临床研究的回顾,并对CAR-T细胞治疗原发性肝癌面临的挑战及解决措施进行汇总。为未来CAR-T细胞疗法在肝癌领域的临床发展提供参考。

Primary liver cancer(PLC)has the features of insidious onset and difficulties in early diagnosis,with limited and ineffective therapeutic options.Chimeric antigen receptor(CAR)T-cell therapy is a genetically modified T-cell therapy that recognizes tumor-specific antigens and activates T cells to exert a tumor-killing effect.CAR T-cell therapy has made great progress in the treatment of hematological tumors and has achieved a good clinical effect in the field of solid tumors in recent years,and although CAR T-cell therapy has developed from the first to the fifth generation,there are still many challenges in the field of solid tumors.This article comprehensively reviews the mechanisms of CAR T-cell therapy for PLC and related research advances,including the main targets such as GPC3,AFP,MUC1,and NKG2D in CAR T-cell therapy for PLC,CAR T-cell therapy for PLC and oncolytic virus,and combined treatment with immune checkpoint inhibitors,as well as the advances in the biological,preclinical,and clinical studies on these targets and treatment modalities and the challenges and solutions for CAR T-cell therapy in the treatment of PLC,so as to provide a reference for the future clinical development of CAR T-cell therapy in liver cancer.