NYMC Faculty Publications

Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes

Yaya Chu, Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
Jordan Milner, Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
Margaret Lamb, Department of Hematology/Oncology/Bone Marrow Transplant, Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, Columbus, Ohio, USA.
Elena Maryamchik, Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Olivia Rigot, Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
Janet Ayello, Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
Lauren Harrison, Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
Rosemarie Shaw, Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
Gregory K. Behbehani, Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, Ohio, USA.
Elaine R. Mardis, Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
Katherine Miller, The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Lakshmi Prakruthi Rao Venkata, The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Hsiaochi Chang, Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, Ohio, USA.
Dean Lee, Department of Hematology/Oncology/Bone Marrow Transplant, Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, Columbus, Ohio, USA.
Elana Rosenthal, Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
Stephan Kadauke, Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Nancy Bunin, Perlman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Julie-An Talano, Department of Pediatrics, Hematology/Oncology and BMT, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Bryon Johnson, Department of Medicine, Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Yongping Wang, Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Mitchell S. Cairo, Department of Pediatrics, New York Medical College, Valhalla, New York, USA.

Author Type(s)

Faculty

Journal Title

The Journal of Infectious Diseases

First Page

788

Last Page

799

Document Type

Article

Publication Date

3-28-2023

Department

Pediatrics

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.

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