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标题：Effective chimeric antigen receptor T cells against SARS-CoV-2
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作者：Xueyang Guo ; Alexandra Kazanova ; Stephanie Thurmond 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：11
页码：1-26
DOI：10.1016/j.isci.2021.103295
语种：English
出版社：Elsevier
摘要：SummaryCurrent therapies to treat coronavirus disease 2019 (COVID-19) involve vaccines against the spike protein S1 of SARS-CoV-2. Here, we outline an alternative approach involving chimeric antigen receptors (CARs) in T cells (CAR-Ts). CAR-T recognition of the SARS-CoV-2 receptor-binding domain (RBD) peptide induced ribosomal protein S6 phosphorylation, the increased expression of activation antigen, CD69 and effectors, interferon-γ, granzyme B, perforin, and Fas-ligand on overlapping subsets of CAR-Ts. CAR-Ts further showed potentin vitrokilling of target cells loaded with RBD, S1 peptide, or expressing the S1 protein. The efficacy of killing varied with different sized hinge regions, whereas time-lapse microscopy showed CAR-T cluster formation around RBD-expressing targets. Cytolysis of targets was mediated primarily by the GZMB/perforin pathway. Lastly, we showedin vivokilling of S1-expressing cells by our SARS-CoV-2 CAR-Ts in mice. The successful generation of SARS-CoV-2 CAR-Ts represents a living vaccine approach for the treatment of COVID-19.Graphical abstractDisplay OmittedHighlights•Cytolytic CAR-Ts can be successfully developed against SARS-CoV-2•CAR-Ts binding to RBD peptide induced effectors IFN-γ, GZMB, Perforin and FasL•CAR-Ts with different hinge regions showed differences in target killing•SARS-CoV-2 CAR-Ts show successfulin vivokilling of S1-expressing cells in miceCell biology; Immunology; Molecular microbiology