Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX, USA.
Immunol Rev. 2014 Jan;257(1):107-26. doi: 10.1111/imr.12131.
Investigators developed chimeric antigen receptors (CARs) for expression on T cells more than 25 years ago. When the CAR is derived from an antibody, the resultant cell should combine the desirable targeting features of an antibody (e.g. lack of requirement for major histocompatibility complex recognition, ability to recognize non-protein antigens) with the persistence, trafficking, and effector functions of a T cell. This article describes how the past two decades have seen a crescendo of research which has now begun to translate these potential benefits into effective treatments for patients with cancer. We describe the basic design of CARs, describe how antigenic targets are selected, and the initial clinical experience with CAR-T cells. Our review then describes our own and other investigators' work aimed at improving the function of CARs and reviews the clinical studies in hematological and solid malignancies that are beginning to exploit these approaches. Finally, we show the value of adding additional engineering features to CAR-T cells, irrespective of their target, to render them better suited to function in the tumor environment, and discuss how the safety of these heavily modified cells may be maintained.
研究人员在 25 年前就开发了可在 T 细胞上表达的嵌合抗原受体（CAR）。当 CAR 来源于抗体时，所得细胞应结合抗体的理想靶向特征（例如不需要主要组织相容性复合体识别，能够识别非蛋白抗原）与 T 细胞的持久性、迁移和效应功能。本文描述了过去二十年中，研究已经逐渐将这些潜在的益处转化为癌症患者的有效治疗方法。我们描述了 CAR 的基本设计，描述了如何选择抗原靶点，以及 CAR-T 细胞的初步临床经验。然后，我们的综述描述了我们自己和其他研究人员旨在改善 CAR 功能的工作，并回顾了正在利用这些方法治疗血液系统恶性肿瘤和实体恶性肿瘤的临床研究。最后，我们展示了为 CAR-T 细胞添加其他工程特征的价值，无论其靶标如何，都可以使它们更适合在肿瘤环境中发挥作用，并讨论如何保持这些经过大量修饰的细胞的安全性。
