美国波士顿大学Wilson W. Wong团队近期取得重要工作进展，他们研究提出了高性能多路药物门控CAR电路系统。该项研究成果2022年9月8日在线发表于《癌细胞》杂志上。
研究人员提出了VIPER CARs（多功能蛋白酶可调节CARs），这是一组用病毒蛋白酶域设计的可诱导ON和OFF开关的CAR电路。他们在异种移植肿瘤和细胞因子释放综合征小鼠模型中，使用FDA批准的抗病毒蛋白酶抑制剂建立了它们的可控性。
此外，研究人员将VIPER CAR与其他药物门控系统进行了基准测试，并展示了同类最佳的性能。他们使用ON VIPER CAR和OFF lenalidomide-CAR系统在体内展示了它们的正交性。最后，研究人员通过结合各种CAR技术设计了几个VIPER CAR环路。他们的多路复用、药物门控CAR电路代表了CAR设计的下一个进展，能够通过先进的逻辑和监管来提高CAR T细胞治疗的安全性。
据介绍，嵌合抗原受体（CAR）T细胞可以彻底改变癌症医学。然而，过度激活，缺乏肿瘤特异性表面标记物和抗原逃逸阻碍了CAR T细胞的发育。需要一种由临床批准的药物调节的多抗原靶向CAR系统。
附：英文原文
Title: High-performance multiplex drug-gated CAR circuits
Author: Hui-Shan Li, Nicole M. Wong, Elliot Tague, John T. Ngo, Ahmad S. Khalil, Wilson W. Wong
Issue&Volume: 2022-09-08
Abstract: Chimeric antigen receptor (CAR) T cells can revolutionize cancer medicine. However,overactivation, lack of tumor-specific surface markers, and antigen escape have hamperedCAR T cell development. A multi-antigen targeting CAR system regulated by clinicallyapproved pharmaceutical agents is needed. Here, we present VIPER CARs (versatile proteaseregulatable CARs), a collection of inducible ON and OFF switch CAR circuits engineeredwith a viral protease domain. We established their controllability using FDA-approvedantiviral protease inhibitors in a xenograft tumor and a cytokine release syndromemouse model. Furthermore, we benchmarked VIPER CARs against other drug-gated systemsand demonstrated best-in-class performance. We showed their orthogonality in vivo using the ON VIPER CAR and OFF lenalidomide-CAR systems. Finally, we engineered severalVIPER CAR circuits by combining various CAR technologies. Our multiplexed, drug-gatedCAR circuits represent the next progression in CAR design capable of advanced logicand regulation for enhancing the safety of CAR T cell therapy.
DOI: 10.1016/j.ccell.2022.08.008
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00372-5
Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
官方网址：https://www.cell.com/cancer-cell/home
投稿链接：https://www.editorialmanager.com/cancer-cell/default.aspx
本期文章：《癌细胞》：Online/在线发表
