Academic Journal
Tacrolimus-resistant SARS-CoV-2-specific T cell products to prevent and treat severe COVID-19 in immunosuppressed patients
| Title: | Tacrolimus-resistant SARS-CoV-2-specific T cell products to prevent and treat severe COVID-19 in immunosuppressed patients |
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| Authors: | Lena Peter, Désirée Jacqueline Wendering, Stephan Schlickeiser, Henrike Hoffmann, Rebecca Noster, Dimitrios Laurin Wagner, Ghazaleh Zarrinrad, Sandra Münch, Samira Picht, Sarah Schulenberg, Hanieh Moradian, Mir-Farzin Mashreghi, Oliver Klein, Manfred Gossen, Toralf Roch, Nina Babel, Petra Reinke, Hans-Dieter Volk, Leila Amini, Michael Schmueck-Henneresse |
| Source: | Molecular Therapy: Methods & Clinical Development, Vol 25, Iss , Pp 52-73 (2022) |
| Publisher Information: | Elsevier, 2022. |
| Publication Year: | 2022 |
| Collection: | LCC:Genetics LCC:Cytology |
| Subject Terms: | solid organ transplant recipients, SARS-CoV-2 infection, COVID-19, adoptive immunotherapy, T cell therapy, CRISPR-Cas9, Genetics, QH426-470, Cytology, QH573-671 |
| More Details: | Solid organ transplant (SOT) recipients receive therapeutic immunosuppression that compromises their immune response to infections and vaccines. For this reason, SOT patients have a high risk of developing severe coronavirus disease 2019 (COVID-19) and an increased risk of death from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Moreover, the efficiency of immunotherapies and vaccines is reduced due to the constant immunosuppression in this patient group. Here, we propose adoptive transfer of SARS-CoV-2-specific T cells made resistant to a common immunosuppressant, tacrolimus, for optimized performance in the immunosuppressed patient. Using a ribonucleoprotein approach of CRISPR-Cas9 technology, we have generated tacrolimus-resistant SARS-CoV-2-specific T cell products from convalescent donors and demonstrate their specificity and function through characterizations at the single-cell level, including flow cytometry, single-cell RNA (scRNA) Cellular Indexing of Transcriptomes and Epitopes (CITE), and T cell receptor (TCR) sequencing analyses. Based on the promising results, we aim for clinical validation of this approach in transplant recipients. Additionally, we propose a combinatory approach with tacrolimus, to prevent an overshooting immune response manifested as bystander T cell activation in the setting of severe COVID-19 immunopathology, and tacrolimus-resistant SARS-CoV-2-specific T cell products, allowing for efficient clearance of viral infection. Our strategy has the potential to prevent severe COVID-19 courses in SOT or autoimmunity settings and to prevent immunopathology while providing viral clearance in severe non-transplant COVID-19 cases. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2329-0501 18184065 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2329050122000286; https://doaj.org/toc/2329-0501 |
| DOI: | 10.1016/j.omtm.2022.02.012 |
| Access URL: | https://doaj.org/article/9113c01efc2341409d18184065607cd5 |
| Accession Number: | edsdoj.9113c01efc2341409d18184065607cd5 |
| Database: | Directory of Open Access Journals |
| ISSN: | 23290501 18184065 |
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| DOI: | 10.1016/j.omtm.2022.02.012 |
| Published in: | Molecular Therapy: Methods & Clinical Development |
| Language: | English |