RT Journal Article SR Electronic T1 Generation of glucocorticoid resistant SARS-CoV-2 T-cells for adoptive cell therapy JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.09.15.298547 DO 10.1101/2020.09.15.298547 A1 Rafet Basar A1 Nadima Uprety A1 Emily Ensley A1 May Daher A1 Kimberly Klein A1 Fernando Martinez A1 Fleur Aung A1 Mayra Shanley A1 Bingqian Hu A1 Elif Gokdemir A1 Mayela Mendt A1 Francia Reyes Silva A1 Sunil Acharya A1 Tamara Laskowski A1 Luis Muniz-Feliciano A1 Pinaki Banerjee A1 Ye Li A1 Sufang Li A1 Luciana Melo Garcia A1 Paul Lin A1 Hila Shaim A1 Sean G. Yates A1 David Marin A1 Indreshpal Kaur A1 Sheetal Rao A1 Duncan Mak A1 Angelique Lin A1 Qi Miao A1 Jinzhuang Dou A1 Ken Chen A1 Richard Champlin A1 Elizabeth J. Shpall A1 Katayoun Rezvani YR 2020 UL http://biorxiv.org/content/early/2020/09/15/2020.09.15.298547.abstract AB Adoptive cell therapy with viral-specific T cells has been successfully used to treat life-threatening viral infections, supporting the application of this approach against COVID-19. We expanded SARS-CoV-2 T-cells from the peripheral blood of COVID-19-recovered donors and non-exposed controls using different culture conditions. We observed that the choice of cytokines modulates the expansion, phenotype and hierarchy of antigenic recognition by SARS-CoV-2 T-cells. Culture with IL-2/4/7 but not other cytokine-driven conditions resulted in >1000 fold expansion in SARS-CoV-2 T-cells with a retained phenotype, function and hierarchy of antigenic recognition when compared to baseline (pre-expansion) samples. Expanded CTLs were directed against structural SARS-CoV-2 proteins, including the receptor-binding domain of Spike. SARS-CoV-2 T-cells could not be efficiently expanded from the peripheral blood of non-exposed controls. Since corticosteroids are used for the management of severe COVID-19, we developed an efficient strategy to inactivate the glucocorticoid receptor gene (NR3C1) in SARS-CoV-2 CTLs using CRISPR-Cas9 gene editing.Competing Interest StatementThe authors have declared no competing interest.