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- Title
Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes.
- Authors
Chu, Yaya; Milner, Jordan; Lamb, Margaret; Maryamchik, Elena; Rigot, Olivia; Ayello, Janet; Harrison, Lauren; Shaw, Rosemarie; Behbehani, Gregory K; Mardis, Elaine R; Miller, Katherine; Venkata, Lakshmi Prakruthi Rao; Chang, Hsiaochi; Lee, Dean; Rosenthal, Elana; Kadauke, Stephan; Bunin, Nancy; Talano, Julie-An; Johnson, Bryon; Wang, Yongping
- Abstract
Background Coronavirus disease 2019 (COVID-19) is caused by 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). Methods Donor screening was done by stimulation of convalescent COVID-19 donor peripheral blood mononuclear cells with viral peptides and identification of interferonγ (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. Results Of the convalescent donor blood samples, 93% passed the screening criteria for clinical manufacture. Three validation runs resulted in enriched T cells that were 79% (standard error of the mean 21%) IFN-γ+ T cells. SARS-CoV-2–vCTLs displayed a highly diverse T-cell receptor 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. Conclusions Highly functional SARS-CoV-2–vCTLs can be rapidly generated by direct cytokine enrichment (12 hours) from convalescent donors. Clinical Trials Registration NCT04896606.
- Subjects
CYTOTOXIC T cells; SARS-CoV-2; MONONUCLEAR leukocytes; TUMOR necrosis factors; COVID-19
- Publication
Journal of Infectious Diseases, 2023, Vol 227, Issue 6, p788
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jiac500