Polyethylene glycol (PEG) is continuing to be a star molecular to increase hydrophilicity and to lengthen the blood circulation after conjugation with therapeutic proteins, nucleotides and nanocarriers. In contrary to the inherent idea, anti-PEG antibodies have been discovered in multiple species after treatment with PEGylated therapeutics. It is even worse that pre-existing anti-PEG antibodies demonstrate increasing prevalence in healthy people without prior exposure to PEGylated therapeutics but reasons underlying await to be clarified. Anti-PEG antibodies, no matter induced or pre-existing, would exert a series of biological effects including but not limited to accelerated blood clearance (ABC) phenomenon, and hypersensitivity reactions after encountering with PEGylated therapeutics, which potentially cause hazards to efficacy and safety of clinical medication. Considering the wide application of PEG in pharmaceutical field, mechanistic understanding on anti-PEG antibodies production and strategies to manage the consequent biological effects are desperately needed. In this review, the prevalence and possible mechanism of anti-PEG antibodies production were outlined. A series of factors that affecting our understanding the impacts of anti-PEG antibodies on in vivo biological effects against PEGylated therapeutics and potential countermeasures were highlighted.

中文翻译：

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抗PEG抗体：现状及对策

聚乙二醇 (PEG) 与治疗性蛋白质、核苷酸和纳米载体结合后，仍然是增加亲水性并延长血液循环的明星分子。与固有的想法相反，在用聚乙二醇化疗法治疗后，在多个物种中发现了抗聚乙二醇抗体。更糟糕的是，预先存在的抗 PEG 抗体在未事先接触过 PEG 化治疗剂的健康人群中的患病率不断增加，但其背后的原因有待澄清。抗PEG抗体，无论是诱导的还是预先存在的，都会产生一系列的生物学效应，包括但不限于加速血液清除（ABC）现象，以及遇到聚乙二醇化治疗后的超敏反应，这可能对疗效和安全性造成危害的临床用药。考虑到 PEG 在制药领域的广泛应用，迫切需要了解抗 PEG 抗体生产的机制以及管理随之而来的生物效应的策略。在这篇综述中，概述了抗 PEG 抗体产生的普遍性和可能的​​机制。强调了影响我们理解抗 PEG 抗体对 PEG 化治疗的体内生物学效应的影响的一系列因素以及潜在的对策。