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10.1016/j.celrep.2021.109432

http://scihub22266oqcxt.onion/10.1016/j.celrep.2021.109432
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34270918!8260499!34270918
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suck abstract from ncbi


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pmid34270918      Cell+Rep 2021 ; 36 (3): 109432
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  • Generation of glucocorticoid-resistant SARS-CoV-2 T cells for adoptive cell therapy #MMPMID34270918
  • Basar R; Uprety N; Ensley E; Daher M; Klein K; Martinez F; Aung F; Shanley M; Hu B; Gokdemir E; Nunez Cortes AK; Mendt M; Reyes Silva F; Acharya S; Laskowski T; Muniz-Feliciano L; Banerjee PP; Li Y; Li S; Melo Garcia L; Lin P; Shaim H; Yates SG; Marin D; Kaur I; Rao S; Mak D; Lin A; Miao Q; Dou J; Chen K; Champlin RE; Shpall EJ; Rezvani K
  • Cell Rep 2021[Jul]; 36 (3): 109432 PMID34270918show ga
  • 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.
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