Glycoprotein Targeted CAR-NK Cells for the Treatment of SARS-CoV-2 Infection

Glycoprotein Targeted CAR-NK Cells for the Treatment of SARS-CoV-2 Infection

H84T-Banana Lectin (BanLec) CAR-NK cells bind high mannose glycosites that decorate the SARS-CoV-2 envelope, thereby decreasing cellular infection in a model of SARS-CoV-2. H84T-BanLec CAR-NK cells are innate effector cells, activated by virus. This novel cellular agent is a promising therapeutic, c...

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Bibliographic Details
Published in:Frontiers in immunology Vol. 12; p. 763460
Main Authors: Christodoulou, Ilias, Rahnama, Ruyan, Ravich, Jonas W, Seo, Jaesung, Zolov, Sergey N, Marple, Andrew N, Markovitz, David M, Bonifant, Challice L
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 23-12-2021
Subjects:
Banana Lectin
CAR-NK cells
Cell Line
Cell- and Tissue-Based Therapy
COVID-19
COVID-19 - therapy
glycobiology
HEK293 Cells
Humans
Immunology
Immunotherapy
Killer Cells, Natural - immunology
Killer Cells, Natural - transplantation
Mannose - metabolism
Musa
Plant Lectins - metabolism
Receptors, Chimeric Antigen - immunology
SARS-CoV-2
SARS-CoV-2 - immunology
Spike Glycoprotein, Coronavirus - immunology
Viral Envelope - immunology
Viral Envelope Proteins - immunology
COVID-19
SARS-CoV-2
Banana Lectin
CAR-NK cells
glycobiology
immunotherapy
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Summary:H84T-Banana Lectin (BanLec) CAR-NK cells bind high mannose glycosites that decorate the SARS-CoV-2 envelope, thereby decreasing cellular infection in a model of SARS-CoV-2. H84T-BanLec CAR-NK cells are innate effector cells, activated by virus. This novel cellular agent is a promising therapeutic, capable of clearing circulating SARS-CoV-2 virus and infected cells. Banana Lectin (BanLec) binds high mannose glycans on viral envelopes, exerting an anti-viral effect. A point mutation (H84T) divorces BanLec mitogenicity from antiviral activity. SARS-CoV-2 contains high mannose glycosites in proximity to the receptor binding domain of the envelope Spike (S) protein. We designed a chimeric antigen receptor (CAR) that incorporates H84T-BanLec as the extracellular moiety. Our H84T-BanLec CAR was devised to specifically direct NK cell binding of SARS-CoV-2 envelope glycosites to promote viral clearance. The H84T-BanLec CAR was stably expressed at high density on primary human NK cells during two weeks of ex vivo expansion. H84T-BanLec CAR-NK cells reduced S-protein pseudotyped lentiviral infection of 293T cells expressing ACE2, the receptor for SARS-CoV-2. NK cells were activated to secrete inflammatory cytokines when in culture with virally infected cells. H84T-BanLec CAR-NK cells are a promising cell therapy for further testing against wild-type SARS-CoV-2 virus in models of SARS-CoV-2 infection. They may represent a viable off-the-shelf immunotherapy for patients suffering from COVID-19.
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Reviewed by: Vincent Vieillard, Centre National de la Recherche Scientifique (CNRS), France; Stephanie Archer-Hartmann, University of Georgia, United States
This article was submitted to NK and Innate Lymphoid Cell Biology, a section of the journal Frontiers in Immunology
Edited by: Evelyn Ullrich, Goethe University Frankfurt, Germany
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.763460