tetano
Editor, Senior Moderator
Cell Rep
. 2021 Jul 7;109432.
doi: 10.1016/j.celrep.2021.109432. Online ahead of print.
Generation of glucocorticoid-resistant SARS-CoV-2 T cells for adoptive cell therapy
Rafet Basar[SUP] 1 [/SUP], Nadima Uprety[SUP] 1 [/SUP], Emily Ensley[SUP] 1 [/SUP], May Daher[SUP] 1 [/SUP], Kimberly Klein[SUP] 2 [/SUP], Fernando Martinez[SUP] 2 [/SUP], Fleur Aung[SUP] 2 [/SUP], Mayra Shanley[SUP] 1 [/SUP], Bingqian Hu[SUP] 1 [/SUP], Elif Gokdemir[SUP] 1 [/SUP], Ana Karen Nunez Cortes[SUP] 1 [/SUP], Mayela Mendt[SUP] 1 [/SUP], Francia Reyes Silva[SUP] 1 [/SUP], Sunil Acharya[SUP] 1 [/SUP], Tamara Laskowski[SUP] 1 [/SUP], Luis Muniz-Feliciano[SUP] 1 [/SUP], Pinaki P Banerjee[SUP] 1 [/SUP], Ye Li[SUP] 1 [/SUP], Sufang Li[SUP] 1 [/SUP], Luciana Melo Garcia[SUP] 1 [/SUP], Paul Lin[SUP] 1 [/SUP], Hila Shaim[SUP] 3 [/SUP], Sean G Yates[SUP] 4 [/SUP], David Marin[SUP] 1 [/SUP], Indreshpal Kaur[SUP] 1 [/SUP], Sheetal Rao[SUP] 1 [/SUP], Duncan Mak[SUP] 5 [/SUP], Angelique Lin[SUP] 5 [/SUP], Qi Miao[SUP] 6 [/SUP], Jinzhuang Dou[SUP] 6 [/SUP], Ken Chen[SUP] 6 [/SUP], Richard E Champlin[SUP] 1 [/SUP], Elizabeth J Shpall[SUP] 1 [/SUP], Katayoun Rezvani[SUP] 7 [/SUP]
Affiliations
Abstract
Adoptive cell therapy with virus-specific T cells has been used successfully to treat life-threatening viral infections, supporting application of this approach to coronavirus disease 2019 (COVID-19). We expand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T cells from the peripheral blood of COVID-19-recovered donors and non-exposed controls using different culture conditions. We observe that the choice of cytokines modulates the expansion, phenotype, and hierarchy of antigenic recognition by SARS-CoV-2 T cells. Culture with interleukin (IL)-2/4/7, but not under other cytokine-driven conditions, results in more than 1,000-fold expansion in SARS-CoV-2 T cells with a retained phenotype, function, and hierarchy of antigenic recognition compared with baseline (pre-expansion) samples. Expanded cytotoxic T lymphocytes (CTLs) are directed against structural SARS-CoV-2 proteins, including the receptor-binding domain of Spike. SARS-CoV-2 T cells cannot be expanded efficiently from the peripheral blood of non-exposed controls. Because corticosteroids are used for management of severe COVID-19, we propose an efficient strategy to inactivate the glucocorticoid receptor gene (NR3C1) in SARS-CoV-2 CTLs using CRISPR-Cas9 gene editing.
Keywords: CRISPR-Cas9; CTL expansion; SARS-CoV-2; adoptive cell therapy; convalescent plasma; glucocorticoid receptor.
. 2021 Jul 7;109432.
doi: 10.1016/j.celrep.2021.109432. Online ahead of print.
Generation of glucocorticoid-resistant SARS-CoV-2 T cells for adoptive cell therapy
Rafet Basar[SUP] 1 [/SUP], Nadima Uprety[SUP] 1 [/SUP], Emily Ensley[SUP] 1 [/SUP], May Daher[SUP] 1 [/SUP], Kimberly Klein[SUP] 2 [/SUP], Fernando Martinez[SUP] 2 [/SUP], Fleur Aung[SUP] 2 [/SUP], Mayra Shanley[SUP] 1 [/SUP], Bingqian Hu[SUP] 1 [/SUP], Elif Gokdemir[SUP] 1 [/SUP], Ana Karen Nunez Cortes[SUP] 1 [/SUP], Mayela Mendt[SUP] 1 [/SUP], Francia Reyes Silva[SUP] 1 [/SUP], Sunil Acharya[SUP] 1 [/SUP], Tamara Laskowski[SUP] 1 [/SUP], Luis Muniz-Feliciano[SUP] 1 [/SUP], Pinaki P Banerjee[SUP] 1 [/SUP], Ye Li[SUP] 1 [/SUP], Sufang Li[SUP] 1 [/SUP], Luciana Melo Garcia[SUP] 1 [/SUP], Paul Lin[SUP] 1 [/SUP], Hila Shaim[SUP] 3 [/SUP], Sean G Yates[SUP] 4 [/SUP], David Marin[SUP] 1 [/SUP], Indreshpal Kaur[SUP] 1 [/SUP], Sheetal Rao[SUP] 1 [/SUP], Duncan Mak[SUP] 5 [/SUP], Angelique Lin[SUP] 5 [/SUP], Qi Miao[SUP] 6 [/SUP], Jinzhuang Dou[SUP] 6 [/SUP], Ken Chen[SUP] 6 [/SUP], Richard E Champlin[SUP] 1 [/SUP], Elizabeth J Shpall[SUP] 1 [/SUP], Katayoun Rezvani[SUP] 7 [/SUP]
Affiliations
- PMID: 34270918
- PMCID: PMC8260499
- DOI: 10.1016/j.celrep.2021.109432
Abstract
Adoptive cell therapy with virus-specific T cells has been used successfully to treat life-threatening viral infections, supporting application of this approach to coronavirus disease 2019 (COVID-19). We expand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T cells from the peripheral blood of COVID-19-recovered donors and non-exposed controls using different culture conditions. We observe that the choice of cytokines modulates the expansion, phenotype, and hierarchy of antigenic recognition by SARS-CoV-2 T cells. Culture with interleukin (IL)-2/4/7, but not under other cytokine-driven conditions, results in more than 1,000-fold expansion in SARS-CoV-2 T cells with a retained phenotype, function, and hierarchy of antigenic recognition compared with baseline (pre-expansion) samples. Expanded cytotoxic T lymphocytes (CTLs) are directed against structural SARS-CoV-2 proteins, including the receptor-binding domain of Spike. SARS-CoV-2 T cells cannot be expanded efficiently from the peripheral blood of non-exposed controls. Because corticosteroids are used for management of severe COVID-19, we propose an efficient strategy to inactivate the glucocorticoid receptor gene (NR3C1) in SARS-CoV-2 CTLs using CRISPR-Cas9 gene editing.
Keywords: CRISPR-Cas9; CTL expansion; SARS-CoV-2; adoptive cell therapy; convalescent plasma; glucocorticoid receptor.