Engineering immunosuppressive drug-resistant armored (IDRA) SARS-CoV-2 T cells for cell therapy
Cell Mol Immunol. 2023 Sep 5. doi: 10.1038/s41423-023-01080-3. Online ahead of print.ABSTRACTSolid 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.PMID:37666955 | DOI:10.1038/s41423-023-01080-3
Source: Cellular and Molecular Immunology - Category: Molecular Biology Authors: Qi Chen Adeline Chia Shou Kit Hang Amy Lim Wee Kun Koh Yanchun Peng Fei Gao Jili Chen Zack Ho Lu-En Wai Kamini Kunasegaran Anthony Tanoto Tan Nina Le Bert Chiew Yee Loh Yun Shan Goh Laurent Renia Tao Dong Anantharaman Vathsala Antonio Bertoletti Source Type: research
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