Virus Induced Lymphocytes (VIL) as a novel viral antigen-specific T cell therapy for COVID-19 and potential future pandemics
Abstract The a priori T cell repertoire and immune response against SARS-CoV-2 viral antigens may explain the varying clinical course and prognosis of patients having a mild COVID-19 infection as opposed to those developing more fulminant multisystem organ failure and associated mortality. Using a n...
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doaj-cecbe836df3548fb9b46236f85e5c7492021-08-01T11:24:41ZengNature Publishing GroupScientific Reports2045-23222021-07-0111111510.1038/s41598-021-94654-yVirus Induced Lymphocytes (VIL) as a novel viral antigen-specific T cell therapy for COVID-19 and potential future pandemicsRohan Sivapalan0Jinyan Liu1Krishnendu Chakraborty2Elisa Arthofer3Modassir Choudhry4Philip S. Barie5Dan H. Barouch6Tom Henley7Intima Bioscience, Inc.Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical SchoolIntima Bioscience, Inc.Intima Bioscience, Inc.Intima Bioscience, Inc.Division of Trauma, Burns, Acute and Critical Care, Department of Surgery; and Division of Medical Ethics, Department of Medicine, Weill Cornell Medicine, New York-Presbyterian Hospital, Weill Cornell Medical CenterCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical SchoolIntima Bioscience, Inc.Abstract The a priori T cell repertoire and immune response against SARS-CoV-2 viral antigens may explain the varying clinical course and prognosis of patients having a mild COVID-19 infection as opposed to those developing more fulminant multisystem organ failure and associated mortality. Using a novel SARS-Cov-2-specific artificial antigen presenting cell (aAPC), coupled with a rapid expansion protocol (REP) as practiced in tumor infiltrating lymphocytes (TIL) therapy, we generate an immune catalytic quantity of Virus Induced Lymphocytes (VIL). Using T cell receptor (TCR)-specific aAPCs carrying co-stimulatory molecules and major histocompatibility complex (MHC) class-I immunodominant SARS-CoV-2 peptide-pentamer complexes, we expand virus-specific VIL derived from peripheral blood mononuclear cells (PBMC) of convalescent COVID-19 patients up to 1000-fold. This is achieved in a clinically relevant 7-day vein-to-vein time-course as a potential adoptive cell therapy (ACT) for COVID-19. We also evaluate this approach for other viral pathogens using Cytomegalovirus (CMV)-specific VIL from donors as a control. Rapidly expanded VIL are enriched in virus antigen-specificity and show an activated, polyfunctional cytokine profile and T effector memory phenotype which may contribute to a robust immune response. Virus-specific T cells can also be delivered allogeneically via MHC-typing and patient human leukocyte antigen (HLA)-matching to provide pragmatic treatment in a large-scale therapeutic setting. These data suggest that VIL may represent a novel therapeutic option that warrants further clinical investigation in the armamentarium against COVID-19 and other possible future pandemics.https://doi.org/10.1038/s41598-021-94654-y |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rohan Sivapalan Jinyan Liu Krishnendu Chakraborty Elisa Arthofer Modassir Choudhry Philip S. Barie Dan H. Barouch Tom Henley |
spellingShingle |
Rohan Sivapalan Jinyan Liu Krishnendu Chakraborty Elisa Arthofer Modassir Choudhry Philip S. Barie Dan H. Barouch Tom Henley Virus Induced Lymphocytes (VIL) as a novel viral antigen-specific T cell therapy for COVID-19 and potential future pandemics Scientific Reports |
author_facet |
Rohan Sivapalan Jinyan Liu Krishnendu Chakraborty Elisa Arthofer Modassir Choudhry Philip S. Barie Dan H. Barouch Tom Henley |
author_sort |
Rohan Sivapalan |
title |
Virus Induced Lymphocytes (VIL) as a novel viral antigen-specific T cell therapy for COVID-19 and potential future pandemics |
title_short |
Virus Induced Lymphocytes (VIL) as a novel viral antigen-specific T cell therapy for COVID-19 and potential future pandemics |
title_full |
Virus Induced Lymphocytes (VIL) as a novel viral antigen-specific T cell therapy for COVID-19 and potential future pandemics |
title_fullStr |
Virus Induced Lymphocytes (VIL) as a novel viral antigen-specific T cell therapy for COVID-19 and potential future pandemics |
title_full_unstemmed |
Virus Induced Lymphocytes (VIL) as a novel viral antigen-specific T cell therapy for COVID-19 and potential future pandemics |
title_sort |
virus induced lymphocytes (vil) as a novel viral antigen-specific t cell therapy for covid-19 and potential future pandemics |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-07-01 |
description |
Abstract The a priori T cell repertoire and immune response against SARS-CoV-2 viral antigens may explain the varying clinical course and prognosis of patients having a mild COVID-19 infection as opposed to those developing more fulminant multisystem organ failure and associated mortality. Using a novel SARS-Cov-2-specific artificial antigen presenting cell (aAPC), coupled with a rapid expansion protocol (REP) as practiced in tumor infiltrating lymphocytes (TIL) therapy, we generate an immune catalytic quantity of Virus Induced Lymphocytes (VIL). Using T cell receptor (TCR)-specific aAPCs carrying co-stimulatory molecules and major histocompatibility complex (MHC) class-I immunodominant SARS-CoV-2 peptide-pentamer complexes, we expand virus-specific VIL derived from peripheral blood mononuclear cells (PBMC) of convalescent COVID-19 patients up to 1000-fold. This is achieved in a clinically relevant 7-day vein-to-vein time-course as a potential adoptive cell therapy (ACT) for COVID-19. We also evaluate this approach for other viral pathogens using Cytomegalovirus (CMV)-specific VIL from donors as a control. Rapidly expanded VIL are enriched in virus antigen-specificity and show an activated, polyfunctional cytokine profile and T effector memory phenotype which may contribute to a robust immune response. Virus-specific T cells can also be delivered allogeneically via MHC-typing and patient human leukocyte antigen (HLA)-matching to provide pragmatic treatment in a large-scale therapeutic setting. These data suggest that VIL may represent a novel therapeutic option that warrants further clinical investigation in the armamentarium against COVID-19 and other possible future pandemics. |
url |
https://doi.org/10.1038/s41598-021-94654-y |
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