Minagawa Kentaro, Zhou Xiaoou, Mineishi Shin, Di Stasi Antonio
Bone Marrow Transplantation and Cellular Therapy, University of Alabama at Birmingham, Birmingham, AL 35294-3300, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030-2399, USA.
Pharmaceuticals (Basel). 2015 May 8;8(2):230-49. doi: 10.3390/ph8020230.
T-cells genetically redirected with a chimeric antigen receptor (CAR) to recognize tumor antigens and kill tumor cells have been infused in several phase 1 clinical trials with success. Due to safety concerns related to on-target/off-tumor effects or cytokine release syndrome, however, strategies to prevent or abate serious adverse events are required. Pharmacologic therapies; suicide genes; or novel strategies to limit the cytotoxic effect only to malignant cells are under active investigations. In this review, we summarize results and toxicities of investigations employing CAR redirected T-cells, with a focus on published strategies to grant safety of this promising cellular application.
通过嵌合抗原受体（CAR）进行基因重定向以识别肿瘤抗原并杀死肿瘤细胞的T细胞已成功用于多项1期临床试验。然而，由于与靶向非肿瘤效应或细胞因子释放综合征相关的安全问题，需要采取预防或减轻严重不良事件的策略。药物治疗、自杀基因或仅将细胞毒性作用限制于恶性细胞的新策略正在积极研究中。在本综述中，我们总结了采用CAR重定向T细胞的研究结果和毒性，重点关注已发表的确保这种有前景的细胞应用安全性的策略。
