@article{PeterWenderingSchlickeiseretal.2022,
  author    = {Peter, Lena and Wendering, D{\´e}sir{\´e}e Jacqueline and Schlickeiser, Stephan and Hoffmann, Henrike and Noster, Rebecca and Wagner, Dimitrios Laurin and Zarrinrad, Ghazaleh and M{\"u}nch, Sandra and Picht, Samira and Schulenberg, Sarah and Moradian, Hanieh and Mashreghi, Mir-Farzin and Klein, Oliver and Gossen, Manfred and Roch, Toralf and Babel, Nina and Reinke, Petra and Volk, Hans-Dieter and Amini, Leila and Schmueck-Henneresse, Michael},
  title     = {Tacrolimus-resistant SARS-CoV-2-specific T cell products to prevent and treat severe COVID-19 in immunosuppressed patients},
  series = {Molecular therapy methods and clinical development},
  volume    = {25},
  journal   = {Molecular therapy methods and clinical development},
  publisher = {Cell Press},
  address   = {Cambridge},
  issn      = {2329-0501},
  doi       = {10.1016/j.omtm.2022.02.012},
  pages     = {52 -- 73},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}