ArticleCellular & molecular immunology2023
Engineering immunosuppressive drug-resistant armored (IDRA) SARS-CoV-2 T cells for cell therapy.
Article in Cellular & molecular immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 4 citations in OpenAlex.
- Engineering "off-the-shelf" TCR-T cells: A transient mRNA platform for balanced alloreactivity and functionality.Molecular therapy. Oncology · 2026Article
- Can Adoptive Immunotherapy With Hepatitis E Virus (HEV)-Specific T Cells Address the Unmet Need in Refractory Chronic HEV Infection?Open forum infectious diseases · 2025Article
- mRNA-Based Engineering of Viral Antigen-Specific TCR-T Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- mRNA-Based Engineering of Viral Antigen-Specific TCR-T Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis.Communications biology · 2024Article
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Solid organ transplant (SOT) recipients receive immunosuppressive drugs (ISDs) and are susceptible to developing severe COVID-19. Here, we analyze the Spike-specific T-cell response after 3 doses of mRNA vaccine in a group of SOT patients (n = 136) treated with different ISDs. We demonstrate that a combination of a calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and prednisone (Pred) treatment regimen strongly suppressed the mRNA vaccine-induced Spike-specific cellular response. Such defects have clinical consequences because the magnitude of vaccine-induced Spike-specific T cells was directly proportional to the ability of SOT patients to rapidly clear SARS-CoV-2 after breakthrough infection. To then compensate for the T-cell defects induced by immunosuppressive treatment and to develop an alternative therapeutic strategy for SOT patients, we describe production of 6 distinct SARS-CoV-2 epitope-specific ISD-resistant T-cell receptor (TCR)-T cells engineered using the mRNA electroporation method with reactivity minimally affected by mutations occurring in Beta, Delta, Gamma, and Omicron variants. This strategy with transient expression characteristics marks an improvement in the immunotherapeutic field and provides an attractive and novel therapeutic possibility for immunosuppressed COVID-19 patients.
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