T cells

SARS-CoV-2-specific T Cells

Phase of research

Potential treatment - pre-clinical evidence

How it helps

Antiviral

Drug status

Used to treat other disease

14
Supporting references
0
Contradictory references
22
Clinical trials

General information

T lymphocyte cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. Groups of specific, differentiated T cell subtypes, such as helper, cytotoxic, memory, and regulatory T (Treg) cells, have a variety of important functions in controlling and shaping the immune response. Memory T cells do appear when T cells recognize a pathogen presented by their local antigen-presenting cells. These T cells activate, proliferate, and differentiate into effector cells secreting compounds to control the infection. Once the pathogen has been cleared, most of the antigen-specific T cells disappear, and a pool of heterogeneous long-lived memory T cells persists. This population of memory T cells, defined as CD45RA or CD45RO+, is maintained over time conferring rapid and long-term immune protection against subsequent reinfections.

Several clinical trials also study the potential of Treg cells in the treatment of conditions including autoimmune diseases, transplant rejection, or graft-versus-host disease (Raffin et al., 2019). The potential of Treg cells in COVID-19 adoptive therapy is being explored, as well.

Current research shows the presence of a SARS-CoV-2 specific T cell population within CD45RA memory T cells from the blood of convalescent donors that can be easily, effectively, and rapidly isolated. These specific SARS-CoV-2 memory T cells may be able to clear virally infected cells and confer T cell immunity for subsequent reinfections. These cells can be stored for use in moderate and severe cases of COVID-19 patients requiring hospitalization, thereby representing an off-the-shelf living drug.

T cells on Wikipedia.

On September 17, 2020, AlloVir, a late clinical-stage cell therapy company, announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug application (IND) for ALVR109, an allogeneic, off-the-shelf virus-specific T cell therapy candidate designed to target SARS-CoV-2. ALVR109 is being developed to arrest the progression of COVID-19 by eradicating SARS-CoV-2 virus-infected cells.


Synonyms

T lymphocytes; T-cell; T Cell Therapy; T memory cells; adoptive cellular therapy; adoptive cell therapy


Supporting references

Link Tested on Impact factor Notes Publication date DB entry date
ALVR109, an off-the-shelf partially HLA matched SARS-CoV-2–specific T cell therapy, to treat refractory severe COVID-19 pneumonia in a heart transplant patient: Case report
ARDS Adoptive cell therapy Case report Mixed substance
An immunosuppressed heart transplant recipient with ARDS 8.09 (2020)

The treatment was safe. The administration of the formulation was followed by decrease (with some variability) of viral loads and alleviation of symptoms (with pulmonary functions not completely returning to the baseline status). Corticosteroid dosing was intentionally lowered during the T cell therapy course. Sample size: 1. Dosage: 2×10^7 cells once every 14 ± 4 days (3 doses total). 

Dec/15/2021 Apr/19/2022
Vaccinated and Convalescent Donor–Derived Severe Acute Respiratory Syndrome Coronavirus 2–Specific T Cells as Adoptive Immunotherapy for High-Risk Coronavirus Disease 2019 Patients
Spike protein Spike variant Cell-based therapy Adoptive cell therapy In vitro Mixed substance
in vitro; Vaccinated individuals or COVID-19 convalescent patients (T cell donors) 9.08 (2020)

SARS-CoV-2 Spike-responsive T cells were expanded from peripheral blood samples of vaccinated (BNT162b2) or COVID-19 convalescent patients (recovered from symptomatic but not critical illness). Using the cell products lysis was successfully induced in a cytotoxicity assay against autologous antigen-pulsed phytohemagglutinin blasts. The T cells responded to stimulation by B.1.1.7 and B.1.351 variant peptides, as well. 

Dec/01/2021 Feb/10/2022
Effective chimeric antigen receptor T cells against SARS-CoV-2
Adoptive cell therapy Animal model Antibody Cell-based therapy In vitro Mixed substance Spike protein
human peripheral blood mononuclear cells (donor material for T cell isolation); Jurkat cells; 293-hACE2(-RBD) cells; NOD-SCID IL2Rγnull mice 5.46 (2020)

Modified T calls expressing a chimeric antigen receptor derived from the CR3022 antibody were prepared. The target antigen (S1 RBD peptide) activated the cells in vitro and led to interferon-γ, granzyme B/perforin, or FasL production in the CD69+ subset of cells. The CAR-T cells effectively killed target cells coated with RBD or S1 antigens in vitro and also S1-expressing cells in a murine model. 

Nov/19/2021 Mar/11/2022
Phase I dose-escalation single centre clinical trial to evaluate the safety of infusion of memory T cells as adoptive therapy in COVID-19 (RELEASE)
Adoptive cell therapy Cell-based therapy Mixed substance Moderate severity Non-randomized non-controlled open trial Phase I clinical trial Severe severity
Moderate to severe COVID-19 patients N/A

SARS-CoV-2-specific CD45RA− memory T cell administration was followed by stabilisation of inflammatory markers. Serious adverse reactions were not observed and clinical improvement (based on an ordinal scale) was noted. Sample size: 3 (low) + 3 (intermediate) + 3 (high). Dosage: 1 × 10^5 cells/kg (low) or 5 × 10^5 cells/kg (intermediate) or 1 × 10^6 cells/kg (high). Main outcome: Safety.

Aug/12/2021 Feb/10/2022
Generation of glucocorticoid-resistant SARS-CoV-2 T cells for adoptive cell therapy
Spike protein Cell-based therapy Adoptive cell therapy In vitro Mixed substance
SARS-CoV-2 PepMix-loaded autologous PBMCs; COVID-19-recovered patients' peripheral blood (source) 9.42 (2020)

SARS-CoV-2-reactive T cells (stimulated with a peptide library derived from various SARS-CoV-2 proteins) were isolated from the peripheral blood of convalescent COVID-19 patients and expanded in culture with IL-2/4/7. A gene knock-out rendering the cells resistant to glucocorticoids was introduced. The cells manifested Th1 cytotoxic phenotype and SARS-CoV-2 PepMix-loaded autologous peripheral blood mononuclear cells-killing capacity in vitro. The T cells were directed mostly against Spike protein. 

Jul/15/2021 Feb/10/2022
Identification of cross-reactive CD8+ T cell receptors with high functional avidity to a SARS-CoV-2 immunodominant epitope and its natural mutant variants
Nucleocapsid protein Cell-based therapy Adoptive cell therapy In vitro Mixed substance
In vitro 7.10 (2020)

A CD8+ T cell epitope on SARS-CoV-2 N protein mediating a robust T cell response was identified. This knowledge was suggested to be utilized in T cell-based adoptive therapy of COVID-19. 

Jun/29/2021 Feb/10/2022
Adoptive transfer of ex vivo expanded SARS-CoV-2-specific cytotoxic lymphocytes: A viable strategy for COVID-19 immunosuppressed patients?
Cell-based therapy Adoptive cell therapy In vitro Mixed substance
in vitro; COVID-19-recovered patients' peripheral blood (source) 2.23 (2020)

SARS-CoV-2 peptide-responsive T cells were expanded from peripheral blood samples of COVID-19 convalescent patients. The cells were proposed for the use in adoptive cell therapy of COVID-19. 

Mar/17/2021 Feb/10/2022
SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell Therapy
Cell-based therapy Adoptive cell therapy
in vitro 5.18

In this study, we report the presence of a SARS-CoV-2 specific T-cell population within CD45RA memory T cells from the blood of convalescent donors that can be easily, effectively, and rapidly isolated by CD45RA depletion. These specific SARS-CoV-2 CD45RA memory T cells may be able to clear virally infected cells and confer T-cell immunity for subsequent reinfections. These cells can be stored for use in moderate and severe cases of COVID-19 patients requiring hospitalization, thereby representing an off-the-shelf living drug.

Feb/25/2021 Apr/22/2021
Rapid GMP-Compliant Expansion of SARS-CoV-2–Specific T Cells From Convalescent Donors for Use as an Allogeneic Cell Therapy for COVID-19
Cell-based therapy Adoptive cell therapy
in vitro 6.43

Donations from individuals who have been infected with SARS-CoV-2 with mild symptoms and have recovered retain normal T cell compartment profiles, with CD4 and CD8 memory and effector T cells specific for SARS-CoV-2 spike, nucleocapsid and membrane antigens. These virus-specific T cells (VSTs) can be isolated using Good Manufacturing Practice (GMP)-compatible selection technology and rapidly expanded in vitro using closed culture vessels and GMP-compliant reagents and medium. The mononuclear cell fraction of a single whole blood donation from a COVID-19 convalescent donor (CCD) can be used to generate up to 1011 T cells within 21 days with the desired central memory phenotype as a potential new therapy for SARS-CoV-2. This offers the potential for the manufacture of a bank of HLA-matched donor T cell products for use in clinical trial and future treatment of COVID-19 patients.

Jan/08/2021 Apr/29/2021
SARS-CoV-2–specific T cells are rapidly expanded for therapeutic use and target conserved regions of the membrane protein
Cell-based therapy Adoptive cell therapy
in vitro 17.54

This study shows that SARS-CoV-2 directed T-cell immunotherapy targeting structural proteins, most importantly membrane protein, should be feasible for the prevention or early treatment of SARS-CoV-2 infection in immunocompromised patients with blood disorders or after bone marrow transplantation to achieve antiviral control while mitigating uncontrolled inflammation.

Dec/17/2020 Apr/22/2021
SARS-CoV-2–specific T cells are rapidly expanded for therapeutic use and target conserved regions of the membrane protein
Spike protein Envelope protein Nucleocapsid protein Adoptive cell therapy In vitro Mixed substance cell-based therapy
In vitro observations-based theory only 22.11 (2020)

T cells recognizing SARS-CoV-2 antigens were successfully expanded (also) from sera of COVID-19 convalescent patients. Multiple CD4-restricted viral epitopes in conserved Spike, Envelope and Nucleocapsid proteins of SARS-CoV-2 were identified. Thus, T cell therapy (after proper MHC matching) was hypothesized to be used as a prevention or an early treatment in immunocompromised patients. 

Dec/17/2020 Apr/19/2022
Using Allogeneic, Off-the-Shelf, Sars-Cov-2-Specific T Cells to Treat High Risk Patients with COVID-19
Preprint
in vitro

SARS-CoV-2-specific T cells generated from convalescent individuals are Th1-polarized, polyfunctional and selectively able to kill viral antigen-expressing targets with no auto- or alloreactivity, indicative of both their selectivity and safety for clinical use.

Dec/07/2020 Apr/30/2021
Rapid production of clinical‐grade SARS‐CoV‐2 specific T cells
Cell-based therapy Adoptive cell therapy
Theory only

High frequencies of rapid antigen-reactive T cells were found in convalescent donors, regardless of severity of COVID-19. The feasibility of clinical-grade production of SARS-CoV-2-specific T cells overnight for therapeutics and diagnostics is revealed.

Jul/12/2020 Apr/22/2021
Harnessing HLA‐E‐restricted CD8 T lymphocytes for adoptive cell therapy of patients with severe COVID‐19
Cell-based therapy Adoptive cell therapy
Theory only 5.52

HLA-restricted and SARS-CoV-2-specific CD8 T cells could be rapidly and cost-effectively prepared in large numbers from COVID-19 convalescent allogeneic donors, banked and used immediately upon request for patients with severe COVID-19.

Jun/01/2020 Apr/30/2021

Clinical trials

ID Title Status Phase Start date Completion date
NCT04762186 Viable Human SARS-CoV-2 Specific T Cell Transfer in Patients at Risk for Severe COVID-19 Recruiting Phase 1 Dec/08/2021 Feb/01/2023
NCT05113862 Evaluation of Safety and Immunogenicity of a T-Cell Priming Peptide Vaccine Against Coronavirus COVID-19 Recruiting Phase 1 Dec/01/2021 Nov/01/2022
NCT04765449 Transfer of Infection Fighting Immune Cells Generated in the Laboratory to High Risk Patients With COVID-19 Infection Recruiting Phase 1 Sep/15/2021 Jul/29/2022
NCT04990557 CRISPR/Cas9-modified Human T Cell ( PD-1and ACE2 Knockout Engineered T Cells ) for Inducing Long-term Immunity in COVID-19 Patients Not yet recruiting Phase 1|Phase 2 Aug/01/2021 Nov/01/2022
NCT05165719 Validation of 'Corona-T-test' for Assessment of SARS-COV-2-specific T-cell Response After COVID-19 or Vaccination Completed Jul/07/2021 Nov/20/2021
NCT04898985 The Leukemia and Lymphoma Society (LLS) T-cells in Blood Cancer and COVID-19 Enrolling by invitation May/20/2021 May/20/2031
NCT04874818 CD8+ T-cell PET/CT Imaging in COVID-19 Patients Not yet recruiting May/01/2021 Sep/01/2022
NCT04852289 A Clinical Observational Study of SARS-CoV-2 Specific CD8 T-Cell Responses to COVID-19 Vaccines in Humans Recruiting Apr/20/2021 Mar/31/2024
NCT05019456 Exercise and COVID-19 Viral T-cell Immunity Recruiting Not Applicable Mar/09/2021 Dec/25/2022
NCT04837651 Humoral and T-Cell Responses to COVID-19 Vaccination in Multiple Sclerosis Patients Treated With Ocrelizumab Treated With Ocrelizumab or Natalizumab Completed Mar/02/2021 Jul/01/2021
NCT04790240 Medical Herbs Inhibit Inflammation Directing T Cells to Kill the COVID-19 Virus (COVID) Recruiting Phase 1|Phase 2 Feb/01/2021 Mar/01/2023
NCT04406064 Viral Specific T-cells for Treatment of COVID-19 Withdrawn Phase 2 Jan/01/2021 Jun/01/2025
NCT04742595 Viral Specific T Cell Therapy for COVID-19 Related Pneumonia Recruiting Early Phase 1 Dec/18/2020 Mar/31/2024
NCT04364828 NGS Diagnostic in COVID-19 Hosts - Genetic Cause Relating to the Course of Disease Progression Recruiting Not Applicable Oct/21/2020 Aug/01/2022
NCT04898140 The Evaluation of Cellular and Humoral Immunity to COVID-19 in Moscow Residents Recruiting Oct/20/2020 Dec/31/2021
NCT04573348 T Cells Response to SARS COV 2 Peptides Recruiting Oct/14/2020 Oct/10/2021
NCT04565067 Identification and Characterization of SARS-CoV-2 Specific CD8 T Cells in Humans Recruiting Sep/22/2020 Sep/20/2022
NCT04578210 Safety Infusion of NatuRal KillEr celLs or MEmory T Cells as Adoptive Therapy in COVID-19 pnEumonia or Lymphopenia Recruiting Phase 1|Phase 2 Sep/04/2020 Mar/01/2021
NCT04470323 Functional Exhaustion of T Cells in COVID19 Patients Recruiting Jul/22/2020 Nov/01/2020
NCT04457726 Part Two of Novel Adoptive Cellular Therapy With SARS-CoV-2 Specific T Cells in Patients With Severe COVID-19 Recruiting Phase 1|Phase 2 Jul/01/2020 Dec/01/2022
NCT04362865 Investigation of the B- and T-cell Repertoire and Immune Response in Patients With Acute and Resolved COVID-19 Infection Recruiting Apr/27/2020 Dec/01/2024
NCT04351659 Novel Adoptive Cellular Therapy With SARS-CoV-2 Specific T Cells in Patients With Severe COVID-19 Recruiting Apr/14/2020 Aug/01/2020