嵌合抗原受体基因修饰的T细胞治疗实体瘤研究进展

Advances in chimeric antigen receptor gene modified T cell therapies for solid tumors

靶向CD19的嵌合抗原受体(CAR)基因修饰的T细胞(CAR-T)在血液肿瘤治疗中取得了巨大成功。然而,迄今为止,由于特异性肿瘤抗原的缺乏、CAR-T细胞难浸润到肿瘤组织内部以及抑制性的肿瘤微环境等因素限制了CAR-T细胞对实体肿瘤的疗效。本文讨论与总结了在CAR-T细胞研究中针对实体瘤的靶点选择、增强免疫细胞向肿瘤迁移、克服肿瘤抑制微环境及联用免疫检查点阻断等新方法、新策略以增加CAR-T细胞对实体肿瘤的疗效,希望对临床前与临床CAR-T细胞治疗实体瘤研究提供新的思路与方向。

Therapy by targeting chimeric antigen receptor(CAR)-modified T cells has made great process progress in hematological malignancies.However,so far,therapeutic effect of CAR-T cells on solid tumors is limited due to the lack of specific tumor antigens,the inability of CAR-T cells to infiltrate into tumors and the inhibitory tumor microenvironment.In this review,we discuss and summarize the novel therapeutic strategies to increase the efficacy of CAR-T cells on solid tumors.These include target selection for solid tumor sites,enhancing the migration of immune cells to tumors sites,overcoming the tumor suppressive microenvironment and combination with immunological checkpoint blockade.We hope to provide new ideas and directions for the preclinical and clinical study on CAR-T therapy of solid tumors.