Feasibility, long-term safety, and immune monitoring of regulatory T cell therapy in living donor kidney transplant recipients - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue American Journal of Transplantation Année : 2021

Feasibility, long-term safety, and immune monitoring of regulatory T cell therapy in living donor kidney transplant recipients

Paul N Harden
Stephan Schlickeiser
  • Fonction : Auteur
Cristiano Scotta
  • Fonction : Auteur
Quizhi Tang
  • Fonction : Auteur
James Markmann
Rachel Hilton
  • Fonction : Auteur

Résumé

Short-term outcomes in kidney transplantation are marred by progressive transplant failure and mortality secondary to immunosuppression toxicity. Immune modulation with autologous polyclonal regulatory T cell (Treg) therapy may facilitate immunosup- pression reduction promoting better long-term clinical outcomes. In a Phase I clini- cal trial, 12 kidney transplant recipients received 1–10 × 106 Treg per kg at Day +5 posttransplantation in lieu of induction immunosuppression (Treg Therapy cohort). Nineteen patients received standard immunosuppression (Reference cohort). Primary outcomes were rejection-free and patient survival. Patient and transplant survival was 100%; acute rejection-free survival was 100% in the Treg Therapy versus 78.9% in the reference cohort at 48 months posttransplant. Treg therapy revealed no excess safety concerns. Four patients in the Treg Therapy cohort had mycophenolate mofetil with - drawn successfully and remain on tacrolimus monotherapy. Treg infusion resulted in a long-lasting dose-dependent increase in peripheral blood Tregs together with an increase in marginal zone B cell numbers. We identified a pretransplantation immune phenotype suggesting a high risk of unsuccessful ex-vivo Treg expansion. Autologous Treg therapy is feasible, safe, and is potentially associated with a lower rejection rate than standard immunosuppression. Treg therapy may provide an exciting opportunity to minimize immunosuppression therapy and improve long-term outcomes
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hal-04641820 , version 1 (09-07-2024)

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Paul N Harden, David S Game, Birgit Sawitzki, Jeroen B van der Net, Joanna Hester, et al.. Feasibility, long-term safety, and immune monitoring of regulatory T cell therapy in living donor kidney transplant recipients. American Journal of Transplantation, 2021, 21 (4), pp.1603 - 1611. ⟨10.1111/ajt.16395⟩. ⟨hal-04641820⟩
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