Hong Lu, Wang Zongkui, Wei Xin, Shi Jianyou, Li Changqing
School of Medicine, University of Electronic Science and Technology of China, Chengdu 611137, China.
Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu 610052, China.
J Pharmacol Toxicol Methods. 2020 Mar-Apr;102:106678. doi: 10.1016/j.vascn.2020.106678. Epub 2020 Jan 23.
Polyethylene glycol (PEG) conjugation, i.e. PEGylation, is a successful strategy to improve the pharmacokinetics and pharmacodynamics of biopharmaceuticals. In the past few decades, PEGylation technology has developed tremendously, and >15 PEGylated therapeutics have been brought to market, with more in development. However, the widely accepted assumption that PEG would have no antigenicity or immunogenicity is increasingly challenged with popularization of PEGylation technique. Although PEGylation indeed reduces the immunogenicities of the modified molecules, and even appears to completely eliminate their immunogenicities, yet emerging clinical evidence of anti-PEG antibodies (including both pre-existing and PEGylated therapeutics-treatment induced anti-PEG antibodies) have been attracted more and more attention. Anti-PEG antibodies were detected in not only patients treated with PEGylated therapeutics but also PEGylated drugs treatment-naïve individuals with a prevalence from <1% to 72%. In patients, the existing anti-PEG antibodies may attenuate therapeutic efficacy of PEGylated drugs and increase adverse effects. Although there is no golden standard avenue, several types of methods, including passive hemagglutination, Western Blot, enzyme linked immunosorbent assay, flow cytometry, Meso Scale Discovery technology, Acoustic Membrane Microparticle assay, and surface plasmon resonace technique, were established and used to screen, confirm and quantitatively detect anti-PEG antibodies. Herein, we focused on reviewing the prevalence of anti-PEG antibodies in healthy and PEGylated therapeutics-treated patients, and highlighting the detection methods for pre-screening and quantitative detection of anti-PEG antibodies.
聚乙二醇（PEG）偶联，即聚乙二醇化，是一种改善生物药物药代动力学和药效学的成功策略。在过去几十年中，聚乙二醇化技术得到了极大发展，已有超过15种聚乙二醇化治疗药物上市，还有更多药物正在研发中。然而，随着聚乙二醇化技术的普及，人们普遍认为PEG没有抗原性或免疫原性这一观点受到了越来越多的挑战。尽管聚乙二醇化确实降低了修饰分子的免疫原性，甚至似乎完全消除了它们的免疫原性，但新出现的抗PEG抗体的临床证据（包括预先存在的和聚乙二醇化治疗药物诱导产生的抗PEG抗体）越来越受到关注。不仅在接受聚乙二醇化治疗药物的患者中检测到了抗PEG抗体，在未接受过聚乙二醇化药物治疗的个体中也检测到了抗PEG抗体，其患病率从<1%到72%不等。在患者中，现有的抗PEG抗体可能会减弱聚乙二醇化药物的治疗效果并增加不良反应。虽然没有黄金标准方法，但已建立并使用了几种类型的方法，包括被动血凝试验、蛋白质印迹法、酶联免疫吸附测定、流式细胞术、Meso Scale Discovery技术、声膜微粒测定法和表面等离子体共振技术，来筛选、确认和定量检测抗PEG抗体。在此，我们重点回顾了健康人群和接受聚乙二醇化治疗药物的患者中抗PEG抗体的患病率，并强调了抗PEG抗体预筛选和定量检测的方法。
