嵌合抗原受体
化学
CD19
抗原
细胞生物学
分子生物学
癌症研究
T细胞
病毒学
生物
免疫学
免疫系统
作者
Wenshe Ray Liu,Wenyue Cao,Zhi Geng,Na Wang,Quan Pan,Shaodong Guo,Jianfeng Zhou,Shiqing Xu
标识
DOI:10.1002/anie.202109550
摘要
As a revolutionary cancer treatment, the chimeric antigen receptor (CAR) T cell therapy suffers from complications such as cytokine release syndromes and T cell exhaustion. Their mitigation desires controllable activation of CAR-T cells that is achievable through regulatory display of CARs. By embedding the hepatitis C virus NS3 protease (HCV-NS3) between the single-chain variable fragment (scFv) and the hinge domain, we showed that the display of anti-CD19 scFv on CAR-T cells was positively correlated to the presence of a clinical HCV-NS3 inhibitor asunaprevir (ASV). This novel CAR design that allows the display of anti-CD19 scFv in the presence of ASV and its removal in the absence of ASV creates a practically reversible chemical switch. We demonstrated that the intact CAR on T cells can be repeatedly turned on and off by controlling the presence of ASV in a dose dependent manner both in vitro and in vivo, which enables delicate modulation of CAR-T activation during cancer treatment.
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