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

Xueyang Guo; Alexandra Kazanova; Stephanie Thurmond; H Uri Saragovi; Christopher E Rudd

doi:10.1016/j.isci.2021.103295

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

iScience. 2021 Nov 19;24(11):103295. doi: 10.1016/j.isci.2021.103295. Epub 2021 Oct 16.

Authors

Xueyang Guo^{1

2

3}, Alexandra Kazanova^{1

2

3}, Stephanie Thurmond^{1

2

3}, H Uri Saragovi⁴, Christopher E Rudd^{1

2

3

5}

Affiliations

¹ Department of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada.
² Department of Microbiology, Infection and Immunology, Universite de Montreal, Montreal, QC H3T 1J4, Canada.
³ Division of Immunology-Oncology, Centre de Researche-Hopital Maisonneuve-Rosemont Hospital (CR-HMR), Montreal, QC H1T 2M4, Canada.
⁴ Lady Davis Institute, Jewish General Hospital, Translational Center for Research in Cancer, McGill University, Montreal, QC, Canada.
⁵ Division of Oncology and Experimental Medicine, McGill University, Montreal, QC, Canada.

Abstract

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.

Keywords: Cell biology; Immunology; Molecular microbiology.