Anti-PEG antibodies: Current situation and countermeasures

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.