Antigen-Specific T Cells and SARS-CoV-2 Infection: Current Approaches and Future Possibilities
Abstract
:1. Introduction
2. Mechanism of Cytokine Storm Development in COVID-19
3. Dysregulation of T Cells in COVID-19
4. SARS-CoV-2-Specific T Cell Therapy for the Treatment and Prevention of Severe COVID-19 Infection
5. Large-Scale Production of SARS-CoV-2-Specific T-Cells
6. Other Potential Cell-Based Therapies for COVID-19
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ADAM17 | A disintegrin and metalloproteinase 1 |
AdV | adenovirus |
Ang | angiotensin |
APC | antigen-presenting cell |
ARDS | acute respiratory distress syndrome |
ATII | alveolar epithelial type II |
AT1R | angiotensin II receptor type 1 |
BALF | bronchoalveolar lavage fluid |
BTLA | B- and T-lymphocyte attenuator |
CAR | chimeric antigen receptor |
CCS | cytokine capture system |
CD25 | cluster of differentiation 25 |
CD4 | cluster of differentiation 4 |
CD8 | cluster of differentiation 8 |
CMV | cytomegalovirus |
COVID-19 | coronavirus disease 2019 |
CST | SARS-CoV-2-specific T cell |
CTLA-4 | cytotoxic T-lymphocyte–associated antigen 4 |
dsRNA | double-stranded RNA |
EBV | Epstein-Barr virus |
EMA | European Medicines Agency |
FDA | The United States Food and Drug Administration |
FOXP3 | forkhead box-p3 |
G-CSF | granulocyte colony-stimulating factor |
GvHD | graft-versus-host disease |
HLA | human leukocyte antigen |
HSCT | hematopoietic stem cell transplantation |
IFN | interferon |
IL | interleukin |
IL-2R | interleukin 2 receptor |
IL-10R | interleukin 10 receptor |
IRF | interferon regulatory factor |
LAG-3 | lymphocyte-activation gene 3 |
MAL | MyD88 adaptor-like protein |
MasR | Mas receptor |
MERS-CoV | Middle East respiratory syndrome coronavirus |
MHC | major histocompatibility complex |
MIS-C | multisystem inflammatory syndrome in children |
MSC | mesenchymal stem cell |
MyD88 | myeloid differentiation primary response protein 88 |
N protein | nucleocapsid protein |
NF-κB | nuclear factor kappa B |
NK cell | natural killer cell |
NKG2A | CD94/NK group 2 member A |
ORF | open reading frame |
PBMCs | peripheral blood mononuclear cells |
PD1 | programmed cell death 1 receptor |
RAS | renin–angiotensin system |
RNA | ribonucleic acid |
S protein | spike protein |
SARS-CoV | severe acute respiratory syndrome coronavirus |
SARS-CoV-1 | severe acute respiratory syndrome coronavirus 1 |
SARS-CoV-2 | severe acute respiratory syndrome coronavirus 2 |
scFv | single chain variable fragment |
ssRNA | single-stranded ribonucleic acid |
TCR | T cell receptor |
TGF-β | transforming growth factor beta |
Tim-3 | T cell immunoglobulin and mucin-domain containing-3 |
TIR | Toll/interleukin receptor |
TLR | Toll-like receptor |
TMPRSS2 | transmembrane serine protease 2 |
TNF-α | tumor necrosis factor α |
TRAM | TRIF-related adaptor molecule |
Treg | regulatory T cell |
TRIF | TIR domain-containing adaptor-inducing interferon-β |
VST | virus-specific T cell |
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Clinical Trial | Therapy | Population Eligibility | Study Design | Phase of Clinical Trial | Estimated Admission | Blood Disorder Exclusion |
---|---|---|---|---|---|---|
NCT04457726 | Allogeneic CSTs | 1 to 90 y SARS-CoV-2 RT-PCR 1 within 72 h of enrollment | Arm A: severe COVID-19 Arm B: mild to moderate COVID-19 with high risk of progression to severe disease based on age and/ or underlying comorbidity | 2/2 (recruiting) | 18 | Not excluded unless receiving 0.5 mg/kg/d steroids |
NCT04765449 | Partially HLA-matched banked allogeneic CSTs | ≥18 y SARS-CoV-2 RT-PCR 1 High risk of severe disease based on age and/or underlying comorbidity No supplemental O2 requirement | Arm A: Treatment with CSTs Arm B: No available HLA-matched product, monitored at home and may receive any standard of care treatment for COVID-19 | 1 (recruiting) | 24 | Included: chemotherapy for malignancy within the prior 24 mo Excluded: prior allogeneic HSCT or solid organ transplant; current chemotherapy, radiation, and/or immunosuppressive drug regimen |
NCT04742595 | Partially HLA-matched banked allogeneic CSTs | ≥18 y Immunocompromised with cancer SARS-CoV-2 RT-PCR 1 within 2 wk of enrollment Presence of respiratory symptoms | Patients receive CSTs on day 1 and treatment may repeat every 14 d at investigators’ discretion. | Early 1 (recruiting) | 16 | No (required for inclusion) |
NCT04762186 | Allogeneic CSTs | Maximum 14 d between symptom onset and enrollment WHO score 5 or 4 with one additional risk factor for progression | Phase I: dose finding phase Phase II: randomized pilot study comparing CST treatment at dose determined in phase I to current institutional standard of care treatment for COVID-19 | 1/2 (recruiting) | 12 | No (inclusion criteria as risk factor for severe disease) |
NCT04896606 | Family derived HLAmatched Allogeneic CSTs | 18 to 65 y SARS-CoV-2 RT-PCR 1 Hospitalized for mild to moderate COVID-19 disease Risk of progression based on underlying comorbidity HLA-matched family related donor with recent SARS-CoV-2 infection at least 10 d from symptom onset available | Experimental arm: Patients receive family donor derived CSTs up to five times every 2 wk along with standard of care. Active Comparator: Standard of care alone. | 2/2 (recruiting) | 50 | No (inclusion criteria as risk factor for severe disease) |
NCT05141058 | HSCT donor-derived allogeneic CSTs | ≥12 y and <80 y ≥28 d and <4 wk after allogeneic HSCT SARS-CoV-2 RT-PCR negative | Arm A: Adults (≥18 to <80 y) will receive a single infusion of CSTs at escalating doses for prophylaxis against SARS-CoV-2 infection. Arm B: Children (≥12 and <18 y) will receive a single infusion of CSTs at escalating doses for prophylaxis against SARS-CoV-2. | 2/2 (recruiting) | 24 | No (required for inclusion) |
NCT04351659 | Blood donation from convalescent donor | 21 to 65 y history of COVID-19 with documented positive test for SARS-CoV-2 in the past; recovered from COVID-19 and is now suitable for blood donation, fulfilling all standard blood donor criteria; Negative test for SARS-CoV-2 currently | Patients receive blood donation from convalescent donor (1 unit) | 1 (recruiting) | 8 | Yes (Do not meet the standard criteria for blood cell donation) |
NCT05447013 | CoV-2-STs generated from COVID-19recovered donors | 18 to 80 yHospitalized patients, SARS-CoV-2 PCR positive, within 8 days from the onset of the symptoms who have: Pneumonia or/and SatO2 ≤ 94% on room air or/and respiratory rate ≥ 24 breaths/min AND Lymphopenia CD3+ ≤ 650/μL or/and ALC ≤ 1000/microl AND Increased values of D-dimers (≥2Χ) or/and ferritin (>1000 ng/mL) or/and CRP (≥3Χ) or/and LDH (≥2Χ) | Experimental: For Phase II: Arm A Standard of care (SOC) and Coronavirus-specific T cells (CoV-2-STs) Active Comparator: For Phase II: Arm B Standard of care (SOC) | 2/2 (recruiting) | 182 | No |
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Nova, Z.; Zemanek, T.; Botek, N. Antigen-Specific T Cells and SARS-CoV-2 Infection: Current Approaches and Future Possibilities. Int. J. Mol. Sci. 2022, 23, 15122. https://doi.org/10.3390/ijms232315122
Nova Z, Zemanek T, Botek N. Antigen-Specific T Cells and SARS-CoV-2 Infection: Current Approaches and Future Possibilities. International Journal of Molecular Sciences. 2022; 23(23):15122. https://doi.org/10.3390/ijms232315122
Chicago/Turabian StyleNova, Zuzana, Tomas Zemanek, and Norbert Botek. 2022. "Antigen-Specific T Cells and SARS-CoV-2 Infection: Current Approaches and Future Possibilities" International Journal of Molecular Sciences 23, no. 23: 15122. https://doi.org/10.3390/ijms232315122