CAR-NK Cells Effectively Target SARS-CoV-2-Spike-Expressing Cell Lines
CAR (chimeric antigen receptor)
COVID-19
E484K variant
N501Y variant
NK cells
SARS-CoV-2
off-the-shelf
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
12
01
2021
accepted:
30
06
2021
entrez:
9
8
2021
pubmed:
10
8
2021
medline:
17
8
2021
Statut:
epublish
Résumé
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is highly contagious and presents a significant public health issue. Current therapies used to treat coronavirus disease 2019 (COVID-19) include monoclonal antibody cocktail, convalescent plasma, antivirals, immunomodulators, and anticoagulants. The vaccines from Pfizer and Moderna have recently been authorized for emergency use, which are invaluable for the prevention of SARS-CoV-2 infection. However, their long-term side effects are not yet documented, and populations with immunocompromised conditions (e.g., organ-transplantation and immunodeficient patients) may not be able to mount an effective immune response. In addition, there are concerns that wide-scale immunity to SARS-CoV-2 may introduce immune pressure that could select for escape mutants to the existing vaccines and monoclonal antibody therapies. Emerging evidence has shown that chimeric antigen receptor (CAR)- natural killer (NK) immunotherapy has potent antitumor response in hematologic cancers with minimal adverse effects in recent studies, however, the potentials of CAR-NK cells in treating COVID-19 has not yet been fully exploited. Here, we improve upon a novel approach for the generation of CAR-NK cells for targeting SARS-CoV-2 and its various mutants. CAR-NK cells were generated using the scFv domain of S309 (henceforward, S309-CAR-NK), a SARS-CoV and SARS-CoV-2 neutralizing antibody (NAbs) that targets the highly conserved region of SARS-CoV-2 spike (S) glycoprotein and is therefore more likely to recognize different variants of SARS-CoV-2 isolates. S309-CAR-NK cells can specifically bind to pseudotyped SARS-CoV-2 virus and its D614G, N501Y, and E484K mutants. Furthermore, S309-CAR-NK cells can specifically kill target cells expressing SARS-CoV-2 S protein
Identifiants
pubmed: 34367128
doi: 10.3389/fimmu.2021.652223
pmc: PMC8343231
doi:
Substances chimiques
Receptors, Chimeric Antigen
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
652223Subventions
Organisme : NHLBI NIH HHS
ID : R21 HL125018
Pays : United States
Organisme : NIH HHS
ID : P51 OD011104
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL150852
Pays : United States
Organisme : NIH HHS
ID : S10 OD025182
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI130197
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI129594
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI124769
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2021 Ma, Badeti, Chen, Kim, Choudhary, Honnen, Reichman, Calianese, Pinter, Jiang, Shi, Zhou, Xu, Li, Gause and Liu.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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