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.
【저자키워드】 immunology, Applied immunology, Biotechnology, 【초록키워드】 COVID-19, Treatment, SARS-CoV-2, immune response, therapy, protocol, Mortality, virus, immune, Antigen, Peripheral blood, lymphocyte, T cell, Clinical course, COVID-19 infection, therapeutic, Patient, Pandemics, phenotype, Mild, cytomegalovirus, PBMC, T cell receptor, MHC, cytokine profile, Donor, Pragmatic, therapeutic option, leukocyte, mononuclear cell, induced, rapid expansion, clinical investigation, aAPC, viral pathogen, effector memory, immunodominant, Multisystem organ failure, approach, Cell, robust, SARS-CoV-2 viral, evaluate, clinically, generate, activated, contribute, complexes, antigen presenting cell, prognosis of patient, co-stimulatory molecule, explain, expand, infiltrating, catalytic, histocompatibility complex, REP, convalescent COVID-19 patient, 【제목키워드】 T cell, Pandemics, induced, therapy for COVID-19,