Sawitzki, Birgit and Harden, Paul N. and Reinke, Petra and Moreau, Aurelie and Hutchinson, James A. and Game, David S. and Tang, Qizhi and Guinan, Eva C. and Battaglia, Manuela and Burlingham, William J. and Roberts, Ian S. D. and Streitz, Mathias and Josien, Regis and Boeger, Carsten A. and Scotta, Cristiano and Markmann, James F. and Hester, Joanna L. and Juerchott, Karsten and Braudeau, Cecile and James, Ben and Contreras-Ruiz, Laura and van der Net, Jeroen B. and Bergler, Tobias and Caldara, Rossana and Petchey, William and Edinger, Matthias and Dupas, Nathalie and Kapinsky, Michael and Mutzbauer, Ingrid and Otto, Natalie M. and Oellinger, Robert and Hernandez-Fuentes, Maria P. and Issa, Fadi and Ahrens, Norbert and Meyenberg, Christoph and Karitzky, Sandra and Kunzendorf, Ulrich and Knechtle, Stuart J. and Grinyo, Josep and Morris, Peter J. and Brent, Leslie and Bushell, Andrew and Turka, Laurence A. and Bluestone, Jeffrey A. and Lechler, Robert I. and Schlitt, Hans J. and Cuturi, Maria C. and Schlickeiser, Stephan and Friend, Peter J. and Miloud, Tewfik and Scheffold, Alexander and Secchi, Antonio and Crisalli, Kerry and Kang, Sang-Mo and Hilton, Rachel and Banas, Bernhard and Blancho, Gilles and Volk, Hans-Dieter and Lombardi, Giovanna and Wood, Kathryn J. and Geissler, Edward K. (2020) Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. LANCET, 395 (10237). pp. 1627-1639. ISSN 0140-6736, 1474-547X
Full text not available from this repository. (Request a copy)Abstract
Background Use of cell-based medicinal products (CBMPs) represents a state-of-the-art approach for reducing general immunosuppression in organ transplantation. We tested multiple regulatory CBMPs in kidney transplant trials to establish the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment. Methods The ONE Study consisted of seven investigator-led, single-arm trials done internationally at eight hospitals in France, Germany, Italy, the UK, and the USA (60 week follow-up). Included patients were living-donor kidney transplant recipients aged 18 years and older. The reference group trial (RGT) was a standard-of-care group given basiliximab, tapered steroids, mycophenolate mofetil, and tacrolimus. Six non-randomised phase 1/2A cell therapy group (CTG) trials were pooled and analysed, in which patients received one of six CBMPs containing regulatory T cells, dendritic cells, or macrophages; patient selection and immunosuppression mirrored the RGT, except basiliximab induction was substituted with CBMPs and mycophenolate mofetil tapering was allowed. None of the trials were randomised and none of the individuals involved were masked. The primary endpoint was biopsy-confirmed acute rejection (BCAR) within 60 weeks after transplantation; adverse event coding was centralised. The RTG and CTG trials are registered with ClinicalTrials.gov, NCT01656135, NCT02252055, NCT02085629, NCT02244801, NCT02371434, NCT02129881, and NCT02091232. Findings The seven trials took place between Dec 11, 2012, and Nov 14, 2018. Of 782 patients assessed for eligibility, 130 (17%) patients were enrolled and 104 were treated and included in the analysis. The 66 patients who were treated in the RGT were 73% male and had a median age of 47 years. The 38 patients who were treated across six CTG trials were 71% male and had a median age of 45 years. Standard-of-care immunosuppression in the recipients in the RGT resulted in a 12% BCAR rate (expected range 3.2-18.0). The overall BCAR rate for the six parallel CTG trials was 16%. 15 (40%) patients given CBMPs were successfully weaned from mycophenolate mofetil and maintained on tacrolimus monotherapy. Combined adverse event data and BCAR episodes from all six CTG trials revealed no safety concerns when compared with the RGT. Fewer episodes of infections were registered in CTG trials versus the RGT. Interpretation Regulatory cell therapy is achievable and safe in living-donor kidney transplant recipients, and is associated with fewer infectious complications, but similar rejection rates in the first year. Therefore, immune cell therapy is a potentially useful therapeutic approach in recipients of kidney transplant to minimise the burden of general immunosuppression. Copyright (C) 2020 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | T-CELLS; IMMUNOSUPPRESSION; MINIMIZATION; STRATEGIES; TOLERANCE; MONOCYTES; INFECTION; EXPANSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Abteilung für Nephrologie Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2021 11:20 |
| Last Modified: | 23 Mar 2021 11:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44531 |
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