Department of Medical Microbiology, Amsterdam UMC, AMC, University of Amsterdam , Amsterdam, the Netherlands.
AIMM Therapeutics , Amsterdam, the Netherlands.
MAbs. 2020 Jan-Dec;12(1):1845908. doi: 10.1080/19420862.2020.1845908.
Recent studies have shown the potential of broadly neutralizing antibodies (bnAbs) for HIV-1 treatment. One of the candidate antibodies moving into clinical trials is the bnAb PGDM1400. Here, we studied the therapeutic potency and escape pathways of bnAb PGDM1400 during monovalent therapy in human immune system (HIS) mice using the BG505, REJO, MJ4 and AMC008 virus isolates. PGDM1400 administered during chronic infection caused a modest decrease in viral load in the first week of administration in 7 out of 10 animals, which correlated with the neutralization sensitivity of the viruses to PGDM1400. As expected for monotherapy, viral loads rebounded after about a week and different viral escape pathways were observed, involving the deletion of glycans in the envelope glycoprotein at positions 130 or 160. (Pre)clinical trials should reveal whether PGDM1400 is a useful component of an antibody combination treatment or as part of a tri-specific antibody.
最近的研究表明，广谱中和抗体（bnAb）在 HIV-1 治疗中有应用潜力。正在进入临床试验的候选抗体之一是 bnAb PGDM1400。在这里，我们使用 BG505、REJO、MJ4 和 AMC008 病毒分离株，在人免疫系统（HIS）小鼠中研究了单价治疗期间 bnAb PGDM1400 的治疗效力和逃逸途径。在慢性感染期间给予 PGDM1400，在 10 只动物中的 7 只中，在给药的第一周内导致病毒载量适度下降，这与病毒对 PGDM1400 的中和敏感性相关。正如单药治疗所预期的那样，大约一周后病毒载量反弹，观察到不同的病毒逃逸途径，涉及到包膜糖蛋白位置 130 或 160 的糖基缺失。（临床前）试验将揭示 PGDM1400 是否是抗体联合治疗的有用组成部分，或者是否作为三特异性抗体的一部分。
