嵌合抗原受体T细胞治疗血液肿瘤的发展与应用

Clinical application of CAR-T cells in treatment of hematologic malignancies

目的嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T细胞)疗法对复发难治(relapse or recurrent,R/R)B细胞急性淋巴白血病的显著效果为R/R恶性血液肿瘤的治疗带来了希望。世界各大医院都以进一步提升CAR-T疗效和扩大其受益范围为目的,开展了针对CAR-T细胞结构、配套疗法及毒副作用管理措施的临床实验。目前,在嵌合抗原受体(CAR)结构设计优化、临床使用有效性及安全性提升和促进CAR-T细胞转归续存等方面都有长足进展,CAR-T细胞疗法临床运用的流程渐渐清晰,针对并发症的有效应对手段也逐渐丰富。但是在对某些疾病(如急性髓系白血病)的探索中,也不乏结果不尽如人意的临床研究,这为CAR-T疗法的进一步发展提出了挑战。面对这些挑战,需从制备到临床运用的各个角度出发,分析成败的原因,不断改进优化,才能最终把握成败。本文就近年来CAR-T细胞疗法在血液恶性肿瘤治疗中的发展动向及走向与临床亟需解决的问题一一梳理,并做出展望。

The stunning benefits of chimeric antigen receptor T(CAR-T)cell therapy in treatment of relapsed and/or refractory(R/R)B cell acute lymphoblastic leukemia have brought hope to the patients with R/R hematologic malignancies.With the aims of achieving more effective and more accessible CAR-T cell therapy,large-scale hospitals all over the world have launched clinical trails by adjusting the CAR structure,complementary treatment and management of side-effects.Great progresses had been made in the CAR structure optimization,efficiency and safety of clinical application,and transformation and survival of CAR-T cells.The process of clinical application of CAR-T cell therapy is gradually clear,and the effective measures for complications are gradually enriched.However,there still are some disappointing outcomes from clinical trails aimed at acute myeloblastic leukemia(AML),which are the challenges badly in need of solutions.In order to finally grasp the success or failure,we must analyze the causes in multiple aspects,from preparation to clinical application,and continuously improve and optimize.In this paper,we sorted out the development trend of CAR-T cell therapy and problems needing be urgently solved in the treatment of hematological malignancies in recent years,and made the prospect for the future.