Zhang Peng, Sun Fang, Liu Sijun, Jiang Shaoyi
Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States.
Department of Bioengineering, University of Washington, Seattle, WA 98195, United States.
J Control Release. 2016 Dec 28;244(Pt B):184-193. doi: 10.1016/j.jconrel.2016.06.040. Epub 2016 Jun 28.
The technique of attaching the polymer polyethylene glycol (PEG), or PEGylation, has brought more than ten protein drugs into market. The surface conjugation of PEG on proteins prolongs their blood circulation time and reduces immunogenicity by increasing their hydrodynamic size and masking surface epitopes. Despite this success, an emerging body of literature highlights the presence of antibodies produced by the immune system that specifically recognize and bind to PEG (anti-PEG Abs), including both pre-existing and treatment-induced Abs. More importantly, the existence of anti-PEG Abs has been correlated with loss of therapeutic efficacy and increase in adverse effects in several clinical reports examining different PEGylated therapeutics. To better understand the nature of anti-PEG immunity, we summarize a number of clinical reports and some critical animal studies regarding pre-existing and treatment-induced anti-PEG Abs. Various anti-PEG detection methods used in different studies were provided. Several protein modification technologies beyond PEGylation were also highlighted.
连接聚合物聚乙二醇（PEG）的技术，即聚乙二醇化，已使十多种蛋白质药物进入市场。蛋白质表面的PEG共轭延长了它们的血液循环时间，并通过增加其流体动力学尺寸和掩盖表面表位来降低免疫原性。尽管取得了这一成功，但越来越多的文献强调免疫系统产生的抗体的存在，这些抗体能特异性识别并结合PEG（抗PEG抗体），包括预先存在的和治疗诱导产生的抗体。更重要的是，在一些研究不同聚乙二醇化疗法的临床报告中，抗PEG抗体的存在与治疗效果丧失和不良反应增加有关。为了更好地理解抗PEG免疫的本质，我们总结了一些关于预先存在的和治疗诱导产生的抗PEG抗体的临床报告以及一些关键的动物研究。提供了不同研究中使用的各种抗PEG检测方法。还强调了聚乙二醇化以外的几种蛋白质修饰技术。
