Clinical and Experimental Immunotherapy Group, Department of Medical Oncology, Institute of Cancer Sciences, The University of Manchester, Manchester Academic Healthcare Science Centre, Manchester, UK; Targeted Therapy Group, Institute of Cancer Sciences, The University of Manchester, Manchester Academic Healthcare Science Centre, Manchester, UK.
Immunol Rev. 2014 Jan;257(1):91-106. doi: 10.1111/imr.12126.
Blockbuster antibody therapies have catapulted immune-based approaches to treat cancer into the consciousness of mainstay clinical research. On the back of this, other emerging immune-based therapies are providing great promise. T-cell therapy is one such area where recent trials using T cells genetically modified to express an antibody-based chimeric antigen receptor (CAR) targeted against the CD19 antigen have demonstrated impressive responses when adoptively transferred to patients with advanced chronic lymphocytic leukemia. The general concept of the CAR T cell was devised some 20 years ago. In this relatively short period of time, the technology to redirect T-cell function has moved at pace facilitating clinical translation; however, many questions remain with respect to developing the approach to improve CAR T-cell therapeutic activity and also to broaden the range of tumors that can be effectively targeted by this approach. This review highlights some of the underlying principles and compromises of CAR T-cell technology using the CD19-targeted CAR as a paradigm and discusses some of the issues that relate to targeting solid tumors with CAR T cells.
重磅抗体疗法将基于免疫的癌症治疗方法推向了主流临床研究的意识前沿。在此基础上，其他新兴的基于免疫的疗法也带来了巨大的希望。T 细胞疗法就是一个这样的领域，最近的临床试验使用经过基因改造表达针对 CD19 抗原的抗体嵌合抗原受体 (CAR) 的 T 细胞进行过继转移，在治疗晚期慢性淋巴细胞白血病患者时显示出令人印象深刻的反应。CAR T 细胞的一般概念是在大约 20 年前提出的。在这相对较短的时间内，重新定向 T 细胞功能的技术发展迅速，促进了临床转化；然而，在提高 CAR T 细胞治疗活性和扩大该方法可有效靶向的肿瘤范围方面，仍有许多问题亟待解决。本综述以靶向 CD19 的 CAR 为例，强调了 CAR T 细胞技术的一些基本原理和折衷方案，并讨论了与使用 CAR T 细胞靶向实体瘤相关的一些问题。
