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. FUNDING The 7th EU Framework Programme.

中文翻译：

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肾移植中的调节细胞疗法（ONE 研究）：七项非随机、单臂、1/2A 期试验的协调设计和分析。

背景技术基于细胞的医药产品（CBMP）的使用代表了用于减少器官移植中的一般免疫抑制的最先进的方法。我们在肾移植试验中测试了多种监管 CBMP，以确定监管 CBMP 与减少的免疫抑制治疗相结合时的安全性。方法 ONE 研究包括七项由研究者主导的单组试验，在法国、德国、意大利、英国和美国的 8 家医院进行（60 周随访）。纳入的患者是 18 岁及以上的活体肾移植受者。参考组试验 (RGT) 是一个标准治疗组，给予巴利昔单抗、逐渐减少的类固醇、吗替麦考酚酯和他克莫司。汇总并分析了六项非随机 1/2A 期细胞治疗组 (CTG) 试验，其中患者接受了六种含有调节性 T 细胞、树突状细胞或巨噬细胞的 CBMP 之一；患者选择和免疫抑制反映了 RGT，除了巴利昔单抗诱导被 CBMP 取代，并且允许吗替麦考酚酯逐渐减量。所有试验都不是随机的，所涉及的个人也没有被掩盖。主要终点是移植后 60 周内活检证实的急性排斥反应 (BCAR)；不良事件编码是集中化的。RTG 和 CTG 试验已在 ClinicalTrials.gov、NCT01656135、NCT02252055、NCT02085629、NCT02244801、NCT02371434、NCT02129881 和 NCT02091232 注册。结果 这七项试验于 2012 年 12 月 11 日至 2018 年 11 月 14 日期间进行。在评估资格的 782 名患者中，130 名 (17%) 患者入组，104 名患者接受治疗并纳入分析。接受 RGT 治疗的 66 名患者中有 73% 为男性，中位年龄为 47 岁。六项 CTG 试验中接受治疗的 38 名患者中有 71% 为男性，中位年龄为 45 岁。RGT 受者的标准护理免疫抑制导致 BCAR 率为 12%（预期范围 3·2-18·0）。六项平行 CTG 试验的总体 BCAR 率为 16%。15 名 (40%) 接受 CBMP 治疗的患者成功戒断霉酚酸酯并维持他克莫司单药治疗。所有六项 CTG 试验的不良事件数据和 BCAR 事件的综合显示，与 RGT 相比，没有安全问题。与 RGT 相比，CTG 试验中记录的感染事件较少。解释 调节性细胞疗法在活体肾移植受者中是可以实现且安全的，并且感染并发症较少，但第一年的排斥率相似。因此，免疫细胞疗法对于肾移植受者来说是一种潜在有用的治疗方法，可以最大限度地减少一般免疫抑制的负担。资助第七个欧盟框架计划。