rsistence of posoleucel was confirmed by T-cell receptor variable β sequencing. Background Kidney transplant recipients with BK virus infection are at risk of developing BK virus–associated nephropathy, allograft rejection, and subsequent graft loss. There are no approved treatments for BK virus infection. Posoleucel is an off-the-shelf, allogeneic, multivirus-specific T-cell investigational therapy targeting BK virus, as well as five other opportunistic viruses: adenovirus, cytomegalovirus, Epstein–Barr virus, human herpesvirus 6, and John Cunningham virus. Methods In this phase 2, double-blind study, kidney transplant recipients with BK viremia were randomized 1:1:1 to receive posoleucel weekly for 3 weeks and then every 14 days (bi-weekly dosing) or every 28 days (monthly dosing) or placebo for 12 weeks. Participants were followed for 12 weeks after completing treatment. The primary objective was safety; the secondary objective was plasma BK viral load reduction. Results Sixty-one participants were randomized and dosed. Baseline characteristics were similar across groups. No deaths, graft-versus-host disease, or cytokine release syndrome occurred. The proportion of patients who had adverse events (AEs) judged by the investigators to be treatment-related was slightly lower in recipients of posoleucel: 20% (4 of 20 patients) and 18% (4 of 22) in those infused on a bi-weekly and monthly schedule, respectively, and 26% (5 of 19) in placebo recipients. None of the grade 3–4 AEs or serious AEs in any group were deemed treatment-related. No deaths, graft-versus-host disease, or cytokine release syndrome occurred. Three participants had allograft rejection, but none were deemed treatment-related by investigators. In posoleucel recipients, BK viremia reduction was associated with an increase in the circulating frequency of BK virus–specific T cells, and the presence and persistence of posoleucel was confirmed by T-cell receptor sequencing. Conclusions Posoleucel was generally safe, well tolerated, and associated with a larger reduction of BK viremia compared with placebo. Limitations of this study include the relatively short duration of follow-up and lack of power to detect significant differences in clinical outcomes. Clinical Trial registry name and registration number: Study of Posoleucel (Formerly Known as ALVR105; Viralym-M) in Kidney Transplant Patients With BK Viremia, NCT04605484....

中文翻译：

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Posoleucel 在患有 BK 病毒血症的肾移植受者中的应用：多中心、随机、双盲、安慰剂对照 2 期试验

通过 T 细胞受体可变 β 测序证实了 posoleucel 的耐药性。背景 感染 BK 病毒的肾移植受者有发生 BK 病毒相关性肾病、同种异体移植物排斥和随后的移植物丢失的风险。目前尚无批准的 BK 病毒感染治疗方法。 Posoleucel 是一种现成的、同种异体、多病毒特异性 T 细胞研究疗法，针对 BK 病毒以及其他五种机会性病毒：腺病毒、巨细胞病毒、Epstein-Barr 病毒、人类疱疹病毒 6 和 John Cunningham 病毒。方法 在这项 2 期双盲研究中，患有 BK 病毒血症的肾移植受者以 1:1:1 的比例随机接受 posoleucel，持续 3 周，每周接受一次 posoleucel，然后每 14 天（每两周给药一次）或每 28 天（每月给药一次）或安慰剂 12 周。完成治疗后，对参与者进行了 12 周的随访。主要目标是安全；次要目标是降低血浆 BK 病毒载量。结果 61 名参与者被随机分配并接受给药。各组的基线特征相似。没有发生死亡、移植物抗宿主病或细胞因子释放综合征。接受 Posoleucel 治疗的患者中，发生被研究人员判断为与治疗相关的不良事件 (AE) 的患者比例略低：双输注患者中为 20%（20 名患者中的 4 名）和 18%（22 名患者中的 4 名） - 安慰剂接受者分别为每周和每月计划，26%（19 人中的 5 人）。任何组中的 3-4 级 AE 或严重 AE 均不被视为与治疗相关。没有发生死亡、移植物抗宿主病或细胞因子释放综合征。三名参与者出现同种异体移植排斥反应，但研究人员认为没有人与治疗相关。在 posoleucel 受体中，BK 病毒血症的减少与 BK 病毒特异性 T 细胞循环频率的增加有关，并且通过 T 细胞受体测序证实了 posoleucel 的存在和持续存在。结论 Posoleucel 总体上是安全的，耐受性良好，并且与安慰剂相比，BK 病毒血症的减少幅度更大。这项研究的局限性包括随访时间相对较短以及缺乏检测临床结果显着差异的能力。临床试验注册名称和注册号：Posoleucel（以前称为 ALVR105；Viralym-M）在患有 BK 病毒血症的肾移植患者中的研究，NCT04605484....