德国雷根斯堡大学Edward K Geissler团队研究了肾移植中进行调节性细胞治疗的效果。该成果发表在2020年5月23日出版的《柳叶刀》杂志上。

细胞药物制剂（CBMPs）的使用是减少器官移植中免疫抑制的最新方法。研究组在肾移植试验中测试了多种调节性CBMP，以确定调节性CBMP结合减少免疫抑制治疗的安全性。

ONE研究包括7项由研究者领导的单臂临床试验，在法国、德国、意大利、英国和美国的8家医院进行。2012年12月11日至2018年11月14日，研究组共招募了130名活体肾移植接受者，最终有104名接受治疗并纳入分析。66名接受标准免疫抑制治疗（参比组试验，RGT），男性占73％，中位年龄为47岁。38名进入六项非随机1 / 2A期细胞治疗组（CTG）试验，接受了六种CBMP治疗，男性占71％，中位年龄为45岁。

移植60周后，RGT组中活检确诊的急性排斥反应（BCAR）发生率为12％，六项平行CTG试验组的总BCAR率为16％。15例（40%）接受CBMPs的患者成功从霉酚酸酯中停药，仅维持他克莫司单药治疗。与RGT相比，所有六项CTG试验的不良事件和BCAR发作的综合结果均显示无安全隐患。与RGT相比，CTG试验中感染事件较少。

总之，调节性细胞治疗在活体肾移植受者中安全可实现，并与较少的感染性并发症相关，但第一年的排斥率相差不大。

附：英文原文

Title: Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials

Author: Birgit Sawitzki, Paul N Harden, Petra Reinke, Aurélie Moreau, James A Hutchinson, David S Game, Qizhi Tang, Eva C Guinan, Manuela Battaglia, William J Burlingham, Ian S D Roberts, Mathias Streitz, Régis Josien, Carsten A Bger, Cristiano Scottà, James F Markmann, Joanna L Hester, Karsten Juerchott, Cecile Braudeau, Ben James, Laura Contreras-Ruiz, Jeroen B van der Net, Tobias Bergler, Rossana Caldara, William Petchey, Matthias Edinger, Nathalie Dupas, Michael Kapinsky, Ingrid Mutzbauer, Natalie M Otto, Robert llinger, Maria P Hernandez-Fuentes, Fadi Issa, Norbert Ahrens, Christoph Meyenberg, Sandra Karitzky, Ulrich Kunzendorf, Stuart J Knechtle, Josep Grinyó, Peter J Morris, Leslie Brent, Andrew Bushell, Laurence A Turka, Jeffrey A Bluestone, Robert I Lechler, Hans J Schlitt, Maria C Cuturi, Stephan Schlickeiser, Peter J Friend, Tewfik Miloud, Alexander Scheffold, Antonio Secchi, Kerry Crisalli, Sang-Mo Kang, Rachel Hilton, Bernhard Banas, Gilles Blancho, Hans-Dieter Volk, Giovanna Lombardi, Kathryn J Wood, Edward K Geissler

Issue&Volume: 2020/05/23

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.

DOI: 10.1016/S0140-6736(20)30167-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30167-7/fulltext