| Title: |
Feasibility, long-term safety, and immune monitoring of regulatory T cell therapy in living donor kidney transplant recipients |
| Authors: |
Harden, Paul, N; Game, David, S; Sawitzki, Birgit; van der Net, Jeroen, B; Hester, Joanna; Bushell, Andrew; Issa, Fadi; Brook, Matthew, O; Alzhrani, Alaa; Schlickeiser, Stephan; Scotta, Cristiano; Petchey, William; Streitz, Mathias; Blancho, Gilles; Tang, Quizhi; Markmann, James; Lechler, Robert, I; Roberts, Ian, S D; Friend, Peter, J; Hilton, Rachel; Geissler, Edward, K; Wood, Kathryn, J; Lombardi, Giovanna |
| Contributors: |
Oxford University Hospitals NHS Trust; University of Oxford; Guy's and St Thomas' Hospital London; Charité - UniversitätsMedizin = Berlin University Medicine; London School of Hygiene and Tropical Medicine (LSHTM); Nuffield Department of Surgical Sciences Oxford, UK; Newcastle University Newcastle; Friedrich-Loeffler-Institut (FLI); Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN); Institut de transplantation urologie-néphrologie (ITUN); Université de Nantes (UN)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Massachusetts General Hospital Boston; King‘s College London; University Hospital Regensburg; Fraunhofer Institute for Toxicology and Experimental Medicine (Fraunhofer ITEM); Fraunhofer (Fraunhofer-Gesellschaft); ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016) |
| Source: |
ISSN: 1600-6135. |
| Publisher Information: |
CCSD; Elsevier |
| Publication Year: |
2021 |
| Collection: |
Université de Nantes: HAL-UNIV-NANTES |
| Subject Terms: |
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; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Description: |
International audience ; Short-term outcomes in kidney transplantation are marred by progressive transplantfailure and mortality secondary to immunosuppression toxicity. Immune modulationwith 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 +5posttransplantation in lieu of induction immunosuppression (Treg Therapy cohort).Nineteen patients received standard immunosuppression (Reference cohort). Primaryoutcomes were rejection-free and patient survival. Patient and transplant survival was100%; acute rejection-free survival was 100% in the Treg Therapy versus 78.9% in thereference cohort at 48 months posttransplant. Treg therapy revealed no excess safetyconcerns. Four patients in the Treg Therapy cohort had mycophenolate mofetil with -drawn successfully and remain on tacrolimus monotherapy. Treg infusion resulted ina long-lasting dose-dependent increase in peripheral blood Tregs together with anincrease in marginal zone B cell numbers. We identified a pretransplantation immunephenotype suggesting a high risk of unsuccessful ex-vivo Treg expansion. AutologousTreg therapy is feasible, safe, and is potentially associated with a lower rejection ratethan standard immunosuppression. Treg therapy may provide an exciting opportunityto minimize immunosuppression therapy and improve long-term outcomes |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1111/ajt.16395 |
| Availability: |
https://hal.science/hal-04641820; https://hal.science/hal-04641820v1/document; https://hal.science/hal-04641820v1/file/American%20J%20Transplantation%20-%202020%20-%20Harden%20-%20Feasibility%20long%E2%80%90term%20safety%20and%20immune%20monitoring%20of%20regulatory%20T%20cell.pdf; https://doi.org/10.1111/ajt.16395 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.4F59CED8 |
| Database: |
BASE |