tetano
Editor, Senior Moderator
iScience
. 2021 Oct 16;103295.
doi: 10.1016/j.isci.2021.103295. Online ahead of print.
Effective chimeric antigen receptor T-cells (CAR-Ts) against SARS-CoV-2
Xueyang Guo[SUP] 1 2 3 [/SUP], Alexandra Kazanova[SUP] 1 2 3 [/SUP], Stephanie Thurmond[SUP] 1 2 3 [/SUP], H Uri Saragovi[SUP] 4 [/SUP], Christopher E Rudd[SUP] 1 2 3 5 [/SUP]
Affiliations
Abstract
Current therapies to treat coronavirus disease 2019 (COVID-19) involve vaccines against the spike (S) 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 (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, while 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-T cells in mice. The successful generation of SARS-CoV-2 CAR-Ts represents a living vaccine approach for the treatment of COVID-19.
Keywords: CARs; RBD and S1; SARS–CoV-2.
. 2021 Oct 16;103295.
doi: 10.1016/j.isci.2021.103295. Online ahead of print.
Effective chimeric antigen receptor T-cells (CAR-Ts) against SARS-CoV-2
Xueyang Guo[SUP] 1 2 3 [/SUP], Alexandra Kazanova[SUP] 1 2 3 [/SUP], Stephanie Thurmond[SUP] 1 2 3 [/SUP], H Uri Saragovi[SUP] 4 [/SUP], Christopher E Rudd[SUP] 1 2 3 5 [/SUP]
Affiliations
- PMID: 34693218
- PMCID: PMC8520176
- DOI: 10.1016/j.isci.2021.103295
Abstract
Current therapies to treat coronavirus disease 2019 (COVID-19) involve vaccines against the spike (S) 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 (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, while 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-T cells in mice. The successful generation of SARS-CoV-2 CAR-Ts represents a living vaccine approach for the treatment of COVID-19.
Keywords: CARs; RBD and S1; SARS–CoV-2.