SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell Therapy

Abstract

Syndrome coronavirus 2 (SARS-CoV-2) pandemic is causing a second outbreak significantly delaying the hope for the virus’ complete eradication. In the absence of effective vaccines, we need effective treatments with low adverse effects that can treat hospitalized patients with COVID-19 disease. In this study, we determined the existence of SARS-CoV-2-specific T cells within CD45RA– memory T cells in the blood of convalescent donors. Memory T cells can respond quickly to infection and provide long-term immune protection to reduce the severity of COVID-19 symptoms. Also, CD45RA– memory T cells confer protection from other pathogens encountered by the donors throughout their life. It is of vital importance to resolve other secondary infections that usually develop in patients hospitalized with COVID-19. We found SARS-CoV-2-specific memory T cells in all of the CD45RA– subsets (CD3+, CD4+, and CD8+) and in the central memory and effector memory subpopulations. The procedure for obtaining these cells is feasible, easy to implement for small-scale manufacture, quick and cost-effective, involves minimal manipulation, and has no GMP requirements. This biobank of specific SARS-CoV-2 memory T cells would be immediately available “off-the-shelf” to treat moderate/severe cases of COVID-19, thereby increasing the therapeutic options available for these patients.

A phase I/II dose-escalation multi-center study to evaluate the safety of infusion of natural killer cells or memory T cells as adoptive therapy in coronavirus pneumonia and/or lymphopenia: RELEASE study protocol

“…The lymphopenia induced by COVID-19 constitutes a therapeutic window that may facilitate donor engraftment and viral protection until recovery. We hypothesized that SARS-CoV-2-specific memory T-lymphocytes obtained from convalescent donors recovered from COVID-19 can be used as a passive cell immunotherapy to treat pneumonia and lymphopenia in moderate/severe patients [43]. These memory helper T cells can form a pool of long-lived memory cells, which upon reencountering with their cognate antigen induce enhanced effector function resulting in increased protection of the host.…”

Recent Advances of COVID-19 Modeling Based on Regenerative Medicine

“…Some other drugs are under evaluation such as colchicine, fluvoxamine, and other immunomodulators (Covid- 19 Treatment Guidelines Panel, 2021). COVID-19 specific T lymphocytes as a plasma subset of convalescent donors have shown some progress in this field ( Ferreras et al, 2021 ). Furthermore, RM has made some steps toward COVID-19 treatment.…”

“…At the time of writing this review, around 80 clinical trials are registered in www.clinicaltrials.gov that have utilized cell- based strategies including stem cells (mostly MSCs) and their derivatives (e.g., exosomes), memory T cells, and natural killer (NK) cells for treating COVID-19 and its related organ injuries. However, there are limited data on MSC therapy in pre-clinical studies, especially on models of lung injury of COVID-19 ( Khoury et al, 2020 ; Ramezankhani et al, 2020 ; Ferreras et al, 2021 ; Park et al, 2021 ; Pérez-Martínez et al, 2021 ). Disease modeling ( in vitro, in vivo , or both) is considered to be one of the major components of RM.…”

COVID-19 Pathology on Various Organs and Regenerative Medicine and Stem Cell-Based Interventions

“…These cells can provide a population of cells for lymphopenia condition along with quick reactions to infection. COVID-19 CD45RA- memory T cells also provide immunity against secondary probable infections that may be found in COVID-19-hospitalized individuals ( Ferreras et al, 2021 ). HLA-matched cytotoxic T cells isolated from convalescent patients are other promising approaches for the treatment of COVID-19 same to EBV-specific cytotoxic T cells, which were utilized for EBV + -related lymphomas ( Hanley et al, 2020 ).…”