T cells engineered to express a chimeric antigen receptor (CAR) have re-shaped the way hematological malignancies are treated. Despite the overwhelming early clinical success, CAR-T therapies are associated with severe side-effects, disease relapse and often exhibit limited efficacy. In this Review article we summarize the most recent biotechnological advances that have been developed to enhance the efficacy and specificity of CAR-T therapies, as well as to address the key challenges associated with them. We place particular emphasis on the most recent clinical data that indicate which CAR-T populations are the most relevant to clinical success, and indicate how the molecular structure of the CAR receptor can affect clinical outcome. Finally, we outline what we believe is the next generation of immunotherapies.

经过工程改造以表达嵌合抗原受体（CAR）的T细胞已经改变了血液系统恶性肿瘤的治疗方式。尽管在临床上取得了压倒性的成功，但CAR-T疗法仍伴随着严重的副作用，疾病复发，并且通常显示出有限的疗效。在这篇综述文章中，我们总结了为增强CAR-T疗法的功效和特异性以及应对与之相关的关键挑战而开发的最新生物技术进展。我们特别强调最新的临床数据，这些数据表明哪些CAR-T人群与临床成功最相关，并表明CAR受体的分子结构如何影响临床结果。最后，我们概述了我们认为的下一代免疫疗法。