Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy
Objectives: Evaluation of the feasibility of SARS-CoV-2-specific T cell manufacturing for adoptive T cell transfer in COVID-19 patients at risk to develop severe disease.Methods: Antiviral SARS-CoV-2-specific T cells were detected in blood of convalescent COVID-19 patients following stimulation with...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.867042/full |
| _version_ | 1819023213136445440 |
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| author | Agnes Bonifacius Sabine Tischer-Zimmermann Maria Michela Santamorena Philip Mausberg Josephine Schenk Stephanie Koch Johanna Barnstorf-Brandes Nina Gödecke Jörg Martens Lilia Goudeva Murielle Verboom Jana Wittig Jana Wittig Britta Maecker-Kolhoff Herrad Baurmann Caren Clark Olaf Brauns Martina Simon Peter Lang Oliver A. Cornely Oliver A. Cornely Oliver A. Cornely Oliver A. Cornely Michael Hallek Rainer Blasczyk Dominic Seiferling Philipp Köhler Philipp Köhler Britta Eiz-Vesper |
| author_facet | Agnes Bonifacius Sabine Tischer-Zimmermann Maria Michela Santamorena Philip Mausberg Josephine Schenk Stephanie Koch Johanna Barnstorf-Brandes Nina Gödecke Jörg Martens Lilia Goudeva Murielle Verboom Jana Wittig Jana Wittig Britta Maecker-Kolhoff Herrad Baurmann Caren Clark Olaf Brauns Martina Simon Peter Lang Oliver A. Cornely Oliver A. Cornely Oliver A. Cornely Oliver A. Cornely Michael Hallek Rainer Blasczyk Dominic Seiferling Philipp Köhler Philipp Köhler Britta Eiz-Vesper |
| author_sort | Agnes Bonifacius |
| collection | DOAJ |
| description | Objectives: Evaluation of the feasibility of SARS-CoV-2-specific T cell manufacturing for adoptive T cell transfer in COVID-19 patients at risk to develop severe disease.Methods: Antiviral SARS-CoV-2-specific T cells were detected in blood of convalescent COVID-19 patients following stimulation with PepTivator SARS-CoV-2 Select using Interferon-gamma Enzyme-Linked Immunospot (IFN-γ ELISpot), SARS-CoV-2 T Cell Analysis Kit (Whole Blood) and Cytokine Secretion Assay (CSA) and were characterized with respect to memory phenotype, activation state and cytotoxic potential by multicolor flow cytometry, quantitative real-time PCR and multiplex analyses. Clinical-grade SARS-CoV-2-specific T cell products were generated by stimulation with MACS GMP PepTivator SARS-CoV-2 Select using CliniMACS Prodigy and CliniMACS Cytokine Capture System (IFN-gamma) (CCS). Functionality of enriched T cells was investigated in cytotoxicity assays and by multiplex analysis of secreted cytotoxic molecules upon target recognition.Results: Donor screening via IFN-γ ELISpot allows for pre-selection of potential donors for generation of SARS-CoV-2-specific T cells. Antiviral T cells reactive against PepTivator SARS-CoV-2 Select could be magnetically enriched from peripheral blood of convalescent COVID-19 patients by small-scale CSA resembling the clinical-grade CCS manufacturing process and showed an activated and cytotoxic T cell phenotype. Four clinical-grade SARS-CoV-2-specific T cell products were successfully generated with sufficient cell numbers and purities comparable to those observed in donor pretesting via CSA. The T cells in the generated products were shown to be capable to replicate, specifically recognize and kill target cells in vitro and secrete cytotoxic molecules upon target recognition. Cell viability, total CD3+ cell number, proliferative capacity and cytotoxic potential remained stable throughout storage of up to 72 h after end of leukapheresis.Conclusion: Clinical-grade SARS-CoV-2-specific T cells are functional, have proliferative capacity and target-specific cytotoxic potential. Their function and phenotype remain stable for several days after enrichment. The adoptive transfer of partially matched, viable human SARS-CoV-2-specific T lymphocytes collected from convalescent individuals may provide the opportunity to support the immune system of COVID-19 patients at risk for severe disease. |
| first_indexed | 2024-12-21T04:35:19Z |
| format | Article |
| id | doaj.art-b345e2f41328481eb4b8678e24661d5e |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-21T04:35:19Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-b345e2f41328481eb4b8678e24661d5e2022-12-21T19:15:51ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-04-011010.3389/fbioe.2022.867042867042Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell TherapyAgnes Bonifacius0Sabine Tischer-Zimmermann1Maria Michela Santamorena2Philip Mausberg3Josephine Schenk4Stephanie Koch5Johanna Barnstorf-Brandes6Nina Gödecke7Jörg Martens8Lilia Goudeva9Murielle Verboom10Jana Wittig11Jana Wittig12Britta Maecker-Kolhoff13Herrad Baurmann14Caren Clark15Olaf Brauns16Martina Simon17Peter Lang18Oliver A. Cornely19Oliver A. Cornely20Oliver A. Cornely21Oliver A. Cornely22Michael Hallek23Rainer Blasczyk24Dominic Seiferling25Philipp Köhler26Philipp Köhler27Britta Eiz-Vesper28Hannover Medical School, Institute of Transfusion Medicine and Transplant Engineering, Hannover, GermanyHannover Medical School, Institute of Transfusion Medicine and Transplant Engineering, Hannover, GermanyHannover Medical School, Institute of Transfusion Medicine and Transplant Engineering, Hannover, GermanyHannover Medical School, Institute of Transfusion Medicine and Transplant Engineering, Hannover, GermanyHannover Medical School, Institute of Transfusion Medicine and Transplant Engineering, Hannover, GermanyDeutsche Gesellschaft für Gewebetransplantation, Hannover, GermanyHannover Medical School, Institute of Transfusion Medicine and Transplant Engineering, Hannover, GermanyHannover Medical School, Institute of Transfusion Medicine and Transplant Engineering, Hannover, GermanyHannover Medical School, Institute of Transfusion Medicine and Transplant Engineering, Hannover, GermanyHannover Medical School, Institute of Transfusion Medicine and Transplant Engineering, Hannover, GermanyHannover Medical School, Institute of Transfusion Medicine and Transplant Engineering, Hannover, GermanyDepartment I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, GermanyFaculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, GermanyDepartment of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyMiltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, GermanyDepartment of Pediatric Hematology and Oncology, University Children’s Hospital, University of Tuebingen, Tuebingen, GermanyDepartment I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, GermanyFaculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, GermanyFaculty of Medicine and University Hospital Cologne, Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Cologne, GermanyGerman Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, GermanyDepartment I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, GermanyHannover Medical School, Institute of Transfusion Medicine and Transplant Engineering, Hannover, Germany0Miltenyi Biomedicine GmbH, Bergisch Gladbach, GermanyDepartment I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, GermanyFaculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, GermanyHannover Medical School, Institute of Transfusion Medicine and Transplant Engineering, Hannover, GermanyObjectives: Evaluation of the feasibility of SARS-CoV-2-specific T cell manufacturing for adoptive T cell transfer in COVID-19 patients at risk to develop severe disease.Methods: Antiviral SARS-CoV-2-specific T cells were detected in blood of convalescent COVID-19 patients following stimulation with PepTivator SARS-CoV-2 Select using Interferon-gamma Enzyme-Linked Immunospot (IFN-γ ELISpot), SARS-CoV-2 T Cell Analysis Kit (Whole Blood) and Cytokine Secretion Assay (CSA) and were characterized with respect to memory phenotype, activation state and cytotoxic potential by multicolor flow cytometry, quantitative real-time PCR and multiplex analyses. Clinical-grade SARS-CoV-2-specific T cell products were generated by stimulation with MACS GMP PepTivator SARS-CoV-2 Select using CliniMACS Prodigy and CliniMACS Cytokine Capture System (IFN-gamma) (CCS). Functionality of enriched T cells was investigated in cytotoxicity assays and by multiplex analysis of secreted cytotoxic molecules upon target recognition.Results: Donor screening via IFN-γ ELISpot allows for pre-selection of potential donors for generation of SARS-CoV-2-specific T cells. Antiviral T cells reactive against PepTivator SARS-CoV-2 Select could be magnetically enriched from peripheral blood of convalescent COVID-19 patients by small-scale CSA resembling the clinical-grade CCS manufacturing process and showed an activated and cytotoxic T cell phenotype. Four clinical-grade SARS-CoV-2-specific T cell products were successfully generated with sufficient cell numbers and purities comparable to those observed in donor pretesting via CSA. The T cells in the generated products were shown to be capable to replicate, specifically recognize and kill target cells in vitro and secrete cytotoxic molecules upon target recognition. Cell viability, total CD3+ cell number, proliferative capacity and cytotoxic potential remained stable throughout storage of up to 72 h after end of leukapheresis.Conclusion: Clinical-grade SARS-CoV-2-specific T cells are functional, have proliferative capacity and target-specific cytotoxic potential. Their function and phenotype remain stable for several days after enrichment. The adoptive transfer of partially matched, viable human SARS-CoV-2-specific T lymphocytes collected from convalescent individuals may provide the opportunity to support the immune system of COVID-19 patients at risk for severe disease.https://www.frontiersin.org/articles/10.3389/fbioe.2022.867042/fulladoptive T cell therapyantiviral T cellsimmunotherapySARS-CoV-2COVID-19 |
| spellingShingle | Agnes Bonifacius Sabine Tischer-Zimmermann Maria Michela Santamorena Philip Mausberg Josephine Schenk Stephanie Koch Johanna Barnstorf-Brandes Nina Gödecke Jörg Martens Lilia Goudeva Murielle Verboom Jana Wittig Jana Wittig Britta Maecker-Kolhoff Herrad Baurmann Caren Clark Olaf Brauns Martina Simon Peter Lang Oliver A. Cornely Oliver A. Cornely Oliver A. Cornely Oliver A. Cornely Michael Hallek Rainer Blasczyk Dominic Seiferling Philipp Köhler Philipp Köhler Britta Eiz-Vesper Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy Frontiers in Bioengineering and Biotechnology adoptive T cell therapy antiviral T cells immunotherapy SARS-CoV-2 COVID-19 |
| title | Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy |
| title_full | Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy |
| title_fullStr | Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy |
| title_full_unstemmed | Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy |
| title_short | Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy |
| title_sort | rapid manufacturing of highly cytotoxic clinical grade sars cov 2 specific t cell products covering sars cov 2 and its variants for adoptive t cell therapy |
| topic | adoptive T cell therapy antiviral T cells immunotherapy SARS-CoV-2 COVID-19 |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.867042/full |
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