Effective chimeric antigen receptor T cells against SARS-CoV-2

Summary: Current 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 (...

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Autores principales:	Xueyang Guo, Alexandra Kazanova, Stephanie Thurmond, H. Uri Saragovi, Christopher E. Rudd
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Cell biology Immunology Molecular microbiology Science Q
Acceso en línea:	https://doaj.org/article/92a1ae3a31c64365ad85696fa463ec73
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spelling	oai:doaj.org-article:92a1ae3a31c64365ad85696fa463ec732021-11-20T05:09:34ZEffective chimeric antigen receptor T cells against SARS-CoV-22589-004210.1016/j.isci.2021.103295https://doaj.org/article/92a1ae3a31c64365ad85696fa463ec732021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012645https://doaj.org/toc/2589-0042Summary: Current 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 potent in vitro killing 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 showed in vivo killing 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.Xueyang GuoAlexandra KazanovaStephanie ThurmondH. Uri SaragoviChristopher E. RuddElsevierarticleCell biologyImmunologyMolecular microbiologyScienceQENiScience, Vol 24, Iss 11, Pp 103295- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cell biology Immunology Molecular microbiology Science Q
spellingShingle	Cell biology Immunology Molecular microbiology Science Q Xueyang Guo Alexandra Kazanova Stephanie Thurmond H. Uri Saragovi Christopher E. Rudd Effective chimeric antigen receptor T cells against SARS-CoV-2
description	Summary: Current 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 potent in vitro killing 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 showed in vivo killing 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.
format	article
author	Xueyang Guo Alexandra Kazanova Stephanie Thurmond H. Uri Saragovi Christopher E. Rudd
author_facet	Xueyang Guo Alexandra Kazanova Stephanie Thurmond H. Uri Saragovi Christopher E. Rudd
author_sort	Xueyang Guo
title	Effective chimeric antigen receptor T cells against SARS-CoV-2
title_short	Effective chimeric antigen receptor T cells against SARS-CoV-2
title_full	Effective chimeric antigen receptor T cells against SARS-CoV-2
title_fullStr	Effective chimeric antigen receptor T cells against SARS-CoV-2
title_full_unstemmed	Effective chimeric antigen receptor T cells against SARS-CoV-2
title_sort	effective chimeric antigen receptor t cells against sars-cov-2
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/92a1ae3a31c64365ad85696fa463ec73
work_keys_str_mv	AT xueyangguo effectivechimericantigenreceptortcellsagainstsarscov2 AT alexandrakazanova effectivechimericantigenreceptortcellsagainstsarscov2 AT stephaniethurmond effectivechimericantigenreceptortcellsagainstsarscov2 AT hurisaragovi effectivechimericantigenreceptortcellsagainstsarscov2 AT christophererudd effectivechimericantigenreceptortcellsagainstsarscov2
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Effective chimeric antigen receptor T cells against SARS-CoV-2

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