@article{d27595e7f4ca42ae9b218af648f125ef,
title = "Feasibility, long-term safety, and immune monitoring of regulatory T cell therapy in living donor kidney transplant recipients",
abstract = "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 immunosuppression reduction promoting better long-term clinical outcomes. In a Phase I clinical 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 Four patients in the Treg Therapy cohort had mycophenolate mofetil withdrawn successfully and remain on tacrolimus monotherapy.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.",
keywords = "clinical research/practice, clinical trial, immune regulation, immunosuppression/immune modulation, immunosuppressive regimens – minimization/withdrawal, kidney transplantation/nephrology, kidney transplantation: living donor, monitoring: immune, translational research/science",
author = "Harden, {Paul N.} and Game, {David S.} and Birgit Sawitzki and {Van der Net}, {Jeroen B.} and Joanna Hester and Andrew Bushell and Fadi Issa and Brook, {Matthew O.} and Alaa Alzhrani and Stephan Schlickeiser and Cristiano Scotta and William Petchey and Mathias Streitz and Gilles Blancho and Quizhi Tang and James Markmann and Lechler, {Robert I.} and Roberts, {Ian S.D.} and Friend, {Peter J.} and Rachel Hilton and Geissler, {Edward K.} and Wood, {Kathryn J.} and Giovanna Lombardi",
note = "Funding Information: This work was supported by the ONE Study which was funded by the 7th EU Framework Programme (award 260687). We thank the ONE Study consortium partners for their support, including the international clinical teams and Beckman Coulter Diagnostics for support of the immune monitoring and Koehler eClinical for eCRF support. A special thanks to Ben James of the central clinical trials team in Regensburg, Germany. We would like to thank the GMP team at Guys Hospital, London composed of Andrew Hope, Christopher Fisher, Henrieta Fraser, Sarah Thirkell, Katie Lowe, and Gilliam Lewis for all their work in generating all the cell products used in this clinical trial. In addition for statistical advice from Saskia Eddy and Dr Sama Ayis at the School of Population Health and Environmental Sciences, Kings College, London. We are grateful to David Ahern of NDORMS in Oxford for the CyTOF analysis. This research was partially funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas{\textquoteright} NHS Foundation Trust and King's College London and/or the NIHR Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Welcome Trust as a senior fellowship grant funded the immune monitoring and analysis component of the trial. Publisher Copyright: {\textcopyright} 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2020",
doi = "10.1111/ajt.16395",
language = "English",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
}