The following is a summary of “Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes,” published in the March 2023 issue of Infectious Diseases by Chu, et al.

For a study, researchers sought to investigate the feasibility of generating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-specific cytotoxic T-cell lymphocytes (vCTLs) from convalescent COVID-19 donors using the CliniMACS Cytokine Capture System (CCS) and to characterize these vCTLs. 

Donor screening stimulated peripheral blood mononuclear cells from convalescent COVID-19 donors with viral peptides and identified IFN-γ⁺ CD4 and CD8 T cells using flow cytometry. Clinical-grade SARS-CoV-2–vCTLs were then manufactured using the CliniMACS CCS. The enriched SARS-CoV-2–vCTLs were characterized by T-cell receptor sequencing, mass cytometry, and transcriptome analysis.

The results showed that 93% of convalescent donor blood samples passed the screening criteria for clinical manufacture. The enriched T cells were 79% IFN-γ+ T cells, as validated in three runs. The SARS-CoV-2–vCTLs displayed a highly diverse T-cell receptor repertoire, with the enhancement of both memory CD8 and CD4 T cells, particularly in CD8 T_EM, CD4 T_CM, and CD4 T_EMRA cell subsets. The SARS-CoV-2–vCTLs were polyfunctional, with increased gene expression in T-cell function, interleukin, pathogen defense, and tumor necrosis factor superfamily pathways.

The study concluded that highly functional SARS-CoV-2–vCTLs can be rapidly generated from convalescent donors using direct cytokine enrichment within 12 hours. These vCTLs possess a diverse T-cell receptor repertoire, and polyfunctional properties, which make them a promising modality for COVID-19 treatment.

Reference: academic.oup.com/jid/article/227/6/788/6965956