McCallen Justin, Prybylski John, Yang Qi, Lai Samuel K
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy; ‡UNC/NCSU Joint Department of Biomedical Engineering; and §Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy; UNC/NCSU Joint Department of Biomedical Engineering; and §Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
ACS Biomater Sci Eng. 2017 Aug 14;3(8):1605-1615. doi: 10.1021/acsbiomaterials.7b00147. Epub 2017 Jun 22.
Polyethylene glycol (PEG), a flexible and relatively hydrophilic polymer, is widely used not only in medicine but also in numerous everyday hygiene, food, and skincare products. Recent animal and human studies have shown that antibodies (Abs) that bind PEG can be induced, leading to markedly reduced therapeutic efficacy of PEGylated therapeutics as well as possibly resulting in acute anaphylaxis and hypersensitivity reactions. Because humans are exposed to numerous other synthetic polymers, we sought to investigate whether such "anti-PEG" antibodies may also bind other synthetic polymers, particularly those with structural similarities to PEG. In a screen of six commercially available and two recombinantly produced anti-PEG IgG and IgM antibodies, we found five antibodies (3 IgG and 2 IgM) that readily bind polypropylene glycol (PPG), polytetramethylene ether glycol (PTMEG), and poly-1,4-butylene adipate (PBA). In contrast, none of the eight antibodies bound dextran (DEX) or polyepoxysuccinic acid (PES), and only two exhibited detectable affinity to polyethylenimine (PEI), suggesting that these PEG-binding antibodies likely possibly recognizable accessible C-C-O groups in the polymer backbone. We also observed similar cross-reactivity in plasma of human subjects with high titers of PEG-binding IgG and IgM. These results directly demonstrate potential cross-reactivity of select PEG-binding antibodies, which represents a new category of antidrug antibodies whereby an adverse immune response can be elicited as a result of prior exposures to PEG or other synthetic PEG-like polymers.
聚乙二醇（PEG）是一种具有柔性且相对亲水的聚合物，不仅广泛应用于医学领域，还用于众多日常卫生、食品和护肤品中。最近的动物和人体研究表明，可诱导产生与PEG结合的抗体（Abs），这会导致聚乙二醇化治疗药物的治疗效果显著降低，并可能引发急性过敏反应和超敏反应。由于人类会接触到许多其他合成聚合物，我们试图研究这种“抗PEG”抗体是否也会与其他合成聚合物结合，特别是那些与PEG结构相似的聚合物。在对六种市售和两种重组产生的抗PEG IgG和IgM抗体进行的筛选中，我们发现五种抗体（3种IgG和2种IgM）能轻易结合聚丙二醇（PPG）、聚四亚甲基醚二醇（PTMEG）和聚己二酸-1,4-丁二醇酯（PBA）。相比之下，这八种抗体均未与葡聚糖（DEX）或聚环氧琥珀酸（PES）结合，只有两种对聚乙烯亚胺（PEI）表现出可检测到的亲和力，这表明这些与PEG结合的抗体可能能够识别聚合物主链中可及的C-C-O基团。我们还在具有高滴度PEG结合IgG和IgM的人类受试者血浆中观察到了类似的交叉反应性。这些结果直接证明了某些PEG结合抗体的潜在交叉反应性，这代表了一类新的抗药物抗体，即先前接触PEG或其他合成PEG样聚合物可能会引发不良免疫反应。
