Weber Marcel, Schmitt Simone, Eicher Barbara, Seidenberg Jemima, Rutkauskaite Justina, Stöckli Benedikt, Townsend Catherine, Huynh-Do Uyen, Schachtner Thomas, Delbue Serena, Mäder Armin, Esslinger Christoph, Hillenbrand Matthias
Memo Therapeutics AG, Schlieren Zurich, Zurich, Switzerland.
Division of Nephrology and Hypertension, University Hospital Bern, Bern, Switzerland.
PLoS Pathog. 2025 Jul 18;21(7):e1013122. doi: 10.1371/journal.ppat.1013122. eCollection 2025 Jul.
BK polyomavirus infection poses a significant risk to kidney transplant recipients. Reactivation of dormant virus in the transplanted kidney, triggered by immunosuppression, can lead to BK polyomavirus-associated nephropathy in up to 10% of transplants, often resulting in loss of graft function or even graft loss. Currently, there is no specific treatment that reliably prevents BK polyomavirus-associated nephropathy or halts its progression. Standard of care relies on reducing immunosuppression, allowing the immune system to gradually control the infection but at the risk of provoking rejection episodes and compromising kidney function. This study describes the discovery and characterization of a highly-potent BK polyomavirus-neutralizing antibody, identified from a kidney transplant recipient who displayed rapid clearance of high-level BKPyV-DNAemia. Antibody mAb 319C07 (USAN potravitug) neutralizes all four BK polyomavirus serotypes and recognizes an epitope critical for viral cell attachment. mAb 319C07 is in clinical development for the treatment of BKPyV infection in renal transplant patients (NCT05769582).
BK多瘤病毒感染对肾移植受者构成重大风险。免疫抑制引发移植肾中潜伏病毒的重新激活，在高达10%的移植病例中可导致BK多瘤病毒相关性肾病，常导致移植肾功能丧失甚至移植肾丢失。目前，尚无可靠预防BK多瘤病毒相关性肾病或阻止其进展的特异性治疗方法。护理标准依赖于降低免疫抑制，使免疫系统逐渐控制感染，但有引发排斥反应和损害肾功能的风险。本研究描述了一种高效BK多瘤病毒中和抗体的发现和特性，该抗体是从一名显示高水平BKPyV血症快速清除的肾移植受者中鉴定出来的。单克隆抗体mAb 319C07（通用名potravitug）可中和所有四种BK多瘤病毒血清型，并识别对病毒细胞附着至关重要的表位。mAb 319C07正在进行治疗肾移植患者BKPyV感染的临床试验开发（NCT05769582）。
