CAR-T联合免疫检查点抑制剂或白细胞介素在恶性肿瘤中的研究进展

Advances in CAR-T combined with immune checkpoint inhibitors or interleukins in malignant tumors

嵌合抗原受体T细胞免疫疗法(CAR-T)是目前比较热点的一种肿瘤免疫治疗,CAR-T疗法在血液恶性肿瘤的治疗中取得了显著的成功,但对实体肿瘤的疗效欠佳,可能的原因是实体瘤特有的抑制性肿瘤免疫微环境以及实体瘤的内部克隆异质性。现阶段提出的克服实体瘤对CAR-T治疗的抗性的主要策略是将CAR-T治疗和其他抗肿瘤疗法联合使用,如放疗、化疗、免疫检查点抑制剂、癌症疫苗、细胞因子治疗、溶瘤病毒治疗、CRISPR/Cas9等基因编辑技术。其中CAR-T细胞治疗与免疫检查点抑制剂的组合以及CAR-T细胞治疗与白细胞介素的组合是很有潜力的临床治疗策略。文章分别从CAR-T联合免疫检查点抑制剂治疗、CAR-T联合白介素治疗的疗效、发展前景,以及毒性等方面进行综述。

Chimeric antigen receptor T-cell immunotherapy(CAR-T)is a hot topic of tumor immunotherapy.CAR-T therapy has achieved remarkable success in the treatment of hematologic malignancies,but the efficacy of CAR-T in solid tumors is poor,which may be due to the unique inhibitory tumor immune microenvironment and the internal clonal heterogeneity of solid tumors.The main strategy proposed at this stage to overcome the resistance of solid tumors to CAR-T is the combination of CAR-T with other anti-tumor therapies,such as radiotherapy,chemotherapy,immune checkpoint inhibitors,cancer vaccines,cytokine therapy,oncolytic virus therapy,CRISPR/Cas9 and other gene editing technologies.Among these,the combination of CAR-T cell therapy and immune checkpoint inhibitors and the combination of CAR-T cell therapy and interleukins are promising clinical therapeutic strategies.This article reviews the efficacy,development prospect and toxicity of CAR-T combined with immune checkpoint inhibitors and CAR-T combined with interleukins.