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Generation of glucocorticoid resistant SARS-CoV-2 T-cells for adoptive cell therapy
Rafet Basar; Nadima Uprety; Emily Ensley; May Daher; Kimberly Klein; Fernando Martinez; Fleur Aung; Mayra Shanley; Bingqian Hu; Elif Gokdemir; Mayela Mendt; Francia Reyes Silva; Sunil Acharya; Tamara Laskowski; Luis Muniz-Feliciano; Pinaki Banerjee; Ye Li; Sufang Li; Luciana Melo Garcia; Paul Lin; Hila Shaim; Sean G Yates; David Marin; Indreshpal Kaur; Sheetal Rao; Duncan Mak; Angelique Lin; Qi Miao; Jinzhuang Dou; Ken Chen; Richard Champlin; Elizabeth J Shpall; Katayoun Rezvani.
Afiliação
  • Rafet Basar; The University of Texas, MD Anderson Cancer Center
  • Nadima Uprety; The University of Texas, MD Anderson Cancer Center
  • Emily Ensley; The University of Texas, MD Anderson Cancer Center
  • May Daher; The University of Texas, MD Anderson Cancer Center
  • Kimberly Klein; The University of Texas, MD Anderson Cancer Center
  • Fernando Martinez; The University of Texas, MD Anderson Cancer Center
  • Fleur Aung; The University of Texas, MD Anderson Cancer Center
  • Mayra Shanley; The University of Texas, MD Anderson Cancer Center
  • Bingqian Hu; The University of Texas, MD Anderson Cancer Center
  • Elif Gokdemir; The University of Texas, MD Anderson Cancer Center
  • Mayela Mendt; The University of Texas, MD Anderson Cancer Center
  • Francia Reyes Silva; The University of Texas, MD Anderson Cancer Center
  • Sunil Acharya; The University of Texas, MD Anderson Cancer Center
  • Tamara Laskowski; The University of Texas, MD Anderson Cancer Center
  • Luis Muniz-Feliciano; The University of Texas, MD Anderson Cancer Center
  • Pinaki Banerjee; The University of Texas, MD Anderson Cancer Center
  • Ye Li; The University of Texas, MD Anderson Cancer Center
  • Sufang Li; The University of Texas, MD Anderson Cancer Center
  • Luciana Melo Garcia; The University of Texas, MD Anderson Cancer Center
  • Paul Lin; The University of Texas, MD Anderson Cancer Center
  • Hila Shaim; The University of Texas Medical Branch
  • Sean G Yates; The University of Texas Medical Branch
  • David Marin; The University of Texas, MD Anderson Cancer Center
  • Indreshpal Kaur; The University of Texas, MD Anderson Cancer Center
  • Sheetal Rao; The University of Texas, MD Anderson Cancer Center
  • Duncan Mak; The University of Texas, MD Anderson Cancer Center
  • Angelique Lin; The University of Texas, MD Anderson Cancer Center
  • Qi Miao; The University of Texas, MD Anderson Cancer Center
  • Jinzhuang Dou; The University of Texas, MD Anderson Cancer Center
  • Ken Chen; The University of Texas, MD Anderson Cancer Center
  • Richard Champlin; The University of Texas, MD Anderson Cancer Center
  • Elizabeth J Shpall; The University of Texas, MD Anderson Cancer Center
  • Katayoun Rezvani; The University of Texas, MD Anderson Cancer Center
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-298547
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ABSTRACT
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.
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Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Preprint
Texto completo
Adicionar na Minha BVS
Imprimir
XML
Buscar no Google
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Preprint