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A Novel Cell Therapy for COVID-19 and Potential Future Pandemics: Virus Induced Lymphocytes (VIL)

Rohan Sivapalan, Jinyan Liu, Krishnendu Chakraborty, Elisa Arthofer, Modassir Choudhry, Philip S Barie, Dan H Barouch, Tom Henley
doi: https://doi.org/10.1101/2020.11.26.400390
Rohan Sivapalan
aIntima Bioscience, Inc. New York, NY, USA
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Jinyan Liu
bCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Krishnendu Chakraborty
aIntima Bioscience, Inc. New York, NY, USA
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Elisa Arthofer
aIntima Bioscience, Inc. New York, NY, USA
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Modassir Choudhry
aIntima Bioscience, Inc. New York, NY, USA
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Philip S Barie
dDivision of Trauma, Burns, Acute and Critical Care, Department of Surgery; and Division of Medical Ethics, Department of Medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, Weill Cornell Medicine, New York, NY, USA
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Dan H Barouch
bCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
cRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA
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  • For correspondence: tom@intimabioscience.com dbarouch@bidmc.harvard.edu
Tom Henley
aIntima Bioscience, Inc. New York, NY, USA
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  • For correspondence: tom@intimabioscience.com dbarouch@bidmc.harvard.edu
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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 1,000-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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted November 27, 2020.
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A Novel Cell Therapy for COVID-19 and Potential Future Pandemics: Virus Induced Lymphocytes (VIL)
Rohan Sivapalan, Jinyan Liu, Krishnendu Chakraborty, Elisa Arthofer, Modassir Choudhry, Philip S Barie, Dan H Barouch, Tom Henley
bioRxiv 2020.11.26.400390; doi: https://doi.org/10.1101/2020.11.26.400390
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A Novel Cell Therapy for COVID-19 and Potential Future Pandemics: Virus Induced Lymphocytes (VIL)
Rohan Sivapalan, Jinyan Liu, Krishnendu Chakraborty, Elisa Arthofer, Modassir Choudhry, Philip S Barie, Dan H Barouch, Tom Henley
bioRxiv 2020.11.26.400390; doi: https://doi.org/10.1101/2020.11.26.400390

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