Lichtman Eben I, Dotti Gianpietro
Department of Medicine, University of North Carolina, Chapel Hill, NC; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC.
Transl Res. 2017 Sep;187:59-82. doi: 10.1016/j.trsl.2017.06.011. Epub 2017 Jun 29.
The adoptive transfer of T-lymphocytes modified to express chimeric antigen receptors (CAR-Ts) has produced impressive clinical responses among patients with B-cell malignancies. This has led to a rapid expansion in the number of clinical trials over the past several years. Although CD19-specific CAR-Ts are the most extensively evaluated, CAR-Ts specific for other B-cell-associated targets have also shown promise. However, despite this success, toxicities associated with CAR-T administration remain a significant concern. There continues to be substantial heterogeneity among CAR-T products, and differences in both CAR designs and CAR-T production strategies can substantially affect clinical outcomes. Ongoing clinical studies will further elucidate these differences and many other innovative approaches are being evaluated at the preclinical level. In this review, we will discuss the background and rationale for the use of CAR-Ts, provide an overview of advances in the field, and examine the application of CAR-Ts to the treatment of B-cell malignancies, including a summary of clinical trials published to date.
经改造后表达嵌合抗原受体的T淋巴细胞（CAR-T细胞）的过继性转移已在B细胞恶性肿瘤患者中产生了令人瞩目的临床反应。这导致在过去几年中临床试验数量迅速增加。尽管针对CD19的CAR-T细胞是评估最广泛的，但针对其他B细胞相关靶点的CAR-T细胞也已显示出前景。然而，尽管取得了这一成功，但与CAR-T细胞给药相关的毒性仍然是一个重大问题。CAR-T细胞产品之间仍然存在很大的异质性，CAR设计和CAR-T细胞生产策略的差异都可能极大地影响临床结果。正在进行的临床研究将进一步阐明这些差异，并且许多其他创新方法正在临床前水平进行评估。在本综述中，我们将讨论使用CAR-T细胞的背景和基本原理，概述该领域的进展，并研究CAR-T细胞在B细胞恶性肿瘤治疗中的应用，包括对迄今发表的临床试验的总结。
