CAR-T细胞治疗实体肿瘤的新策略

New strategies for CAR-T cell in the treatment of solid tumors

嵌合型抗原受体修饰T(chimeric antigen receptor modified T,CAR-T)细胞治疗作为一种新的过继性免疫疗法在血液肿瘤中已取得了较好的疗效。在实体肿瘤中,肿瘤微环境中存在大量免疫抑制细胞、免疫抑制分子以及胞外基质,对迁移的CAR-T细胞的细胞毒性效应产生抑制作用,在实体肿瘤内严重抑制CAR-T细胞的抗肿瘤效力。同时,大多数实体肿瘤存在肿瘤异质性且缺乏相对特异性肿瘤抗原,CAR-T细胞在实体肿瘤部位的归巢能力差并伴随着脱靶效应,使其在实体瘤中的疗效欠佳。与血液肿瘤相比,实体瘤具有复杂的生物学特性,需要针对性的策略才能保证CAR-T细胞抗肿瘤长期有效。本文就CAR-T细胞的发展、在实体瘤治疗中的困惑及治疗策略的研究进展作一阐述。

Chimeric antigen receptor modified T（CAR-T） cell, a novel adoptive immunotherapy strategy, has been used successfully against hematological tumors. However, in solid tumors, due to multiple immunosuppressive cells, immunosuppressive molecules, and extracellular matrix play a suppressive role in the cytotoxic effects of migrating CAR-T cells and severely inhibit the antitumor efficacy of CAR-T cells in the tumor microenvironment of solid tumors. Simultaneously, tumor heterogeneity, lacking proper tumor antigens,poor homing ability at solid tumor sites, along with off-target effect, resulting in poor therapeutic effect of CAR-T cells in solid tumors.Compared with hematological tumors, solid tumors have complex biological characteristics, and thus targeted strategies are demanded to ensure long-term efficacy of CAR-T cells against tumors. This review makes a summary of the development of CAR-T cells, the confusion in solid tumors and the progress of treatment strategies.