Cross-Reactivity of Select PEG-Binding Antibodies to Other Polymers Containing a C-C-O Backbone

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.