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A Reversible Chemogenetic Switch for Chimeric Antigen Receptor T Cells**

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单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Hematol, Wuhan, Hubei, Peoples R China [2]Texas A&M Univ, Texas A&M Drug Discovery Lab, Dept Chem, College Stn, TX 77843 USA [3]Texas A&M Univ, Inst Biosci & Technol, Coll Med, Houston, TX 77030 USA [4]Texas A&M Univ, Dept Biochem & Biophys, Houston, TX 77843 USA [5]Texas A&M Univ, Dept Mol & Cellular Med, Coll Med, Houston, TX 77843 USA
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关键词: asunaprevir CAR-T therapy chemical switches chimeric antigen receptors NS3 protease

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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出版当年[2021]版:
大类 | 1 区 化学
小类 | 1 区 化学综合
最新[2025]版:
大类 | 1 区 化学
小类 | 1 区 化学:综合
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出版当年[2020]版:
Q1 CHEMISTRY, MULTIDISCIPLINARY
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Q1 CHEMISTRY, MULTIDISCIPLINARY

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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Hematol, Wuhan, Hubei, Peoples R China [2]Texas A&M Univ, Texas A&M Drug Discovery Lab, Dept Chem, College Stn, TX 77843 USA
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通讯机构: [2]Texas A&M Univ, Texas A&M Drug Discovery Lab, Dept Chem, College Stn, TX 77843 USA [3]Texas A&M Univ, Inst Biosci & Technol, Coll Med, Houston, TX 77030 USA [4]Texas A&M Univ, Dept Biochem & Biophys, Houston, TX 77843 USA [5]Texas A&M Univ, Dept Mol & Cellular Med, Coll Med, Houston, TX 77843 USA
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