Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes. (30th December 2022)

• Record Type: Journal Article
• 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; Prakruthi Rao Venkata, Lakshmi; Chang, Hsiaochi; Lee, Dean; Rosenthal, Elana; Kadauke, Stephan; Bunin, Nancy; Talano, Julie-An; Johnson, Bryon; Wang, Yongping; Cairo, Mitchell S
• Is Part Of: Journal of infectious diseases. Volume 227:Number 6(2023)
• Page Start: 788
• Page End: 799
• Publication Date: 2022-12-30
• Subjects: SARS-CoV-2 -- IFN-γ+ T cells -- TCRB CDR3 repertoire -- cytokine capture system -- immune landscape -- virus-specific cytotoxic T lymphocytes; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiac500
• Languages: English
• ISSNs: 0022-1899

Abstract

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. Abstract : Highly functional SARS-CoV-2–vCTLs can be rapidly generated from convalescent COVID-19 donors using the CliniMACS Cytokine Capture System. SARS-CoV-2–vCTLs displayed a highly diverse TCR repertoire, enhanced memory CD8 and CD4 T cells, and increased gene expression in T-cell function and other pathways.