| Autor: |
Yaya, Chu, Jordan, Milner, Margaret, Lamb, Elena, Maryamchik, Olivia, Rigot, Janet, Ayello, Lauren, Harrison, Rosemarie, Shaw, Gregory K, Behbehani, Elaine R, Mardis, Katherine, Miller, Lakshmi Prakruthi Rao, Venkata, Hsiaochi, Chang, Dean, Lee, Elana, Rosenthal, Stephan, Kadauke, Nancy, Bunin, Julie-An, Talano, Bryon, Johnson, Yongping, Wang, Mitchell S, Cairo |
| Rok vydání: |
2022 |
| Zdroj: |
The Journal of infectious diseases. |
| ISSN: |
1537-6613 |
| Popis: |
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 virus-specific cytotoxic T-cell lymphocytes (vCTLs) could provide a promising modality in COVID-19 treatment. We aimed to screen, manufacture, and characterize SARS-CoV-2-vCTLs generated from convalescent COVID-19 donors using the CliniMACS® Cytokine Capture System (CCS).Donor screening was done by stimulation of convalescent COVID-19 donor peripheral blood mononuclear cells with viral peptides and identification of IFN-γ+ CD4 and CD8 T-cells using flow cytometry. Clinical-grade SARS-CoV-2-vCTLs were manufactured using the CliniMACS® CCS. The enriched SARS-CoV-2-vCTLs were characterized by T-cell receptor sequencing, mass cytometry, and transcriptome analysis.93% of convalescent donor blood samples passed the screening criteria for clinical manufacture. Three validation runs resulted in enriched T-cells that were 79% ± 21% IFN-γ+ T-cells. SARS-CoV-2-vCTLs displayed a highly diverse TCR repertoire with enhancement of both memory CD8 and CD4 T-cells, especially in CD8 TEM, CD4 TCM and CD4 TEMRA cell subsets. SARS-CoV-2-vCTLs were polyfunctional with increased gene expression in T-cell function, interleukin, pathogen defense, and tumor necrosis factor superfamily pathways.Highly functional SARS-CoV-2-vCTLs can be rapidly generated by direct cytokine enrichment (12 hours) from convalescent donors.NCT04896606, NCT03266627, NCT03266640, NCT03266653, NCT04197596. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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