@article{LandwehrKenzelZobelHoffmannetal.2018,
  author    = {Landwehr-Kenzel, Sybille and Zobel, Anne and Hoffmann, Henrike and Landwehr, Niels and Schmueck-Henneresse, Michael and Schachtner, Thomas and Roemhild, Andy and Reinke, Petra},
  title     = {Ex vivo expanded natural regulatory T cells from patients with end-stage renal disease or kidney transplantation are useful for autologous cell therapy},
  series = {Kidney international : official journal of the International Society of Nephrology},
  volume    = {93},
  journal   = {Kidney international : official journal of the International Society of Nephrology},
  number    = {6},
  publisher = {Elsevier},
  address   = {New York},
  issn      = {0085-2538},
  doi       = {10.1016/j.kint.2018.01.021},
  pages     = {1452 -- 1464},
  year      = {2018},
  abstract  = {Novel concepts employing autologous, ex vivo expanded natural regulatory T cells (nTreg) for adoptive transfer has potential to prevent organ rejection after kidney transplantation. However, the impact of dialysis and maintenance immunosuppression on the nTreg phenotype and peripheral survival is not well understood, but essential when assessing patient eligibility. The current study investigates regulatory T-cells in dialysis and kidney transplanted patients and the feasibility of generating a clinically useful nTreg product from these patients. Heparinized blood from 200 individuals including healthy controls, dialysis patients with end stage renal disease and patients 1, 5, 10, 15, 20 years after kidney transplantation were analyzed. Differentiation and maturation of nTregs were studied by flow cytometry in order to compare dialysis patients and kidney transplanted patients under maintenance immunosuppression to healthy controls. CD127 expressing CD4(+)CD25(high)FoxP3(+) nTregs were detectable at increased frequencies in dialysis patients with no negative impact on the nTreg end product quality and therapeutic usefulness of the ex vivo expanded nTregs. Further, despite that immunosuppression mildly altered nTreg maturation, neither dialysis nor pharmacological immunosuppression or previous acute rejection episodes impeded nTreg survival in vivo. Accordingly, the generation of autologous, highly pure nTreg products is feasible and qualifies patients awaiting or having received allogenic kidney transplantation for adoptive nTreg therapy. Thus, our novel treatment approach may enable us to reduce the incidence of organ rejection and reduce the need of long-term immunosuppression.},
  language  = {en}
}
@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}
}