Qin Di-Yuan, Huang Yong, Li Dan, Wang Yong-Sheng, Wang Wei, Wei Yu-Quan
West China Medical School, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Anticancer Drugs. 2016 Sep;27(8):711-22. doi: 10.1097/CAD.0000000000000387.
T-lymphocytes genetically engineered with the chimeric antigen receptor (CAR-T) have shown great therapeutic potential in cancer treatment. A variety of preclinical researches and clinical trials of CAR-T therapy have been carried out to lay the foundation for future clinical application. In these researches, several gene-transfer methods were used to deliver CARs or other genes into T-lymphocytes, equipping CAR-modified T cells with a property of recognizing and attacking antigen-expressing tumor cells in a major histocompatibility complex-independent manner. Here, we summarize the gene-transfer vectors commonly used in the generation of CAR-T cell, including retrovirus vectors, lentivirus vectors, the transposon/transposase system, the plasmid-based system, and the messenger RNA electroporation system. The following aspects were compared in parallel: efficiency of gene transfer, the integration methods in the modified T cells, foreground of scale-up production, and application and development in clinical trials. These aspects should be taken into account to generate the optimal CAR-gene vector that may be suitable for future clinical application.
经嵌合抗原受体（CAR-T）基因工程改造的T淋巴细胞在癌症治疗中显示出巨大的治疗潜力。已经开展了多种CAR-T疗法的临床前研究和临床试验，为未来的临床应用奠定基础。在这些研究中，使用了几种基因转移方法将CAR或其他基因导入T淋巴细胞，使CAR修饰的T细胞具备以主要组织相容性复合体非依赖方式识别和攻击表达抗原的肿瘤细胞的特性。在此，我们总结了CAR-T细胞生成中常用的基因转移载体，包括逆转录病毒载体、慢病毒载体、转座子/转座酶系统、基于质粒的系统和信使核糖核酸电穿孔系统。同时对以下几个方面进行了比较：基因转移效率、修饰T细胞中的整合方法、扩大生产前景以及在临床试验中的应用和发展。在生成可能适用于未来临床应用的最佳CAR基因载体时应考虑这些方面。
