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

• DOI: 10.1111/ajt.16395
• Publication Date: 2020-11-10T22:50:07Z
• Authors: Paul N. Harden; David S. Game; Birgit Sawitzki; Jeroen B. Van der...; Joanna Hester; Andrew Bushell; Fadi Issa; Matthew O. Brook; Alaa Alzhrani; Stephan Schlickeiser; Cristiano Scotta; William Petchey; Mathias Streitz; Gilles Blancho; Quizhi Tang; James Markmann; Robert I. Lechler; Ian S.D. Roberts; Peter J. Friend; Rachel Hilton; Edward K. Geissler; Kathryn J. Wood; Giovanna Lombardi
• Keywords: Cell therapy; Graft rejection

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 reduction promoting better long-term clinical outcomes. In a Phase I trial, 12 recipients received 1–10 × 106 Treg per kg at Day +5 posttransplantation lieu of induction (Treg Therapy cohort). Nineteen patients standard (Reference Primary were rejection-free patient survival. Patient survival was 100%; acute 100% the versus 78.9% reference cohort 48 months posttransplant. revealed no excess safety concerns. Four had mycophenolate mofetil withdrawn successfully remain on tacrolimus monotherapy. infusion resulted long-lasting dose-dependent increase peripheral blood Tregs together an marginal zone B numbers. We identified pretransplantation immune phenotype suggesting high risk unsuccessful ex-vivo expansion. Autologous is feasible, safe, potentially associated lower rejection rate than immunosuppression. provide exciting opportunity minimize improve