Kalinin R S, Petukhov A V, Knorre V D, Maschan M A, Stepanov A V, Gabibov A G
M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str. 16 /10, Moscow, 117997, Russia.
Dmitrii Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Samory Mashela Str. 1, Moscow, 117997, Russia.
Acta Naturae. 2018 Apr-Jun;10(2):16-23.
Chimeric antigen receptor-modified T-cell therapy (CAR-T therapy) is one of the fastest developing areas of immuno-oncology. Over the past decade, it has revolutionized the cell therapy modality and expedited its pace of development, from optimization of the structure of chimeric antigen receptors and animal model experiments to successful clinical application. The initial designs of the CAR configuration focused on increasing T-cell activation, cytotoxicity, and persistence. However, the first attempts to treat patients with CAR T cells have demonstrated the need for increased safety and controlled activation of genetically modified T cells. Herein, we summarize the different molecular approaches to engineering chimeric antigen receptors for reducing the potential clinical risks of T-cell therapy.
嵌合抗原受体修饰的T细胞疗法（CAR-T疗法）是免疫肿瘤学中发展最快的领域之一。在过去十年中，它彻底改变了细胞治疗模式，并加快了其发展步伐，从嵌合抗原受体结构的优化和动物模型实验到成功的临床应用。CAR构型的最初设计侧重于增强T细胞的激活、细胞毒性和持久性。然而，首次用CAR T细胞治疗患者的尝试表明，需要提高基因改造T细胞的安全性并控制其激活。在此，我们总结了工程化嵌合抗原受体以降低T细胞治疗潜在临床风险的不同分子方法。
