title: Anti-PEG antibodies in the clinic: Current issues and beyond PEGylation.
abstract: The technique of attaching the polymer polyethylene glycol (PEG), or PEGylation, has brought more than ten protein drugs into market. The surface conjugation of PEG on proteins prolongs their blood circulation time and reduces immunogenicity by increasing their hydrodynamic size and masking surface epitopes. Despite this success, an emerging body of literature highlights the presence of antibodies produced by the immune system that specifically recognize and bind to PEG (anti-PEG Abs), including both pre-existing and treatment-induced Abs. More importantly, the existence of anti-PEG Abs has been correlated with loss of therapeutic efficacy and increase in adverse effects in several clinical reports examining different PEGylated therapeutics. To better understand the nature of anti-PEG immunity, we summarize a number of clinical reports and some critical animal studies regarding pre-existing and treatment-induced anti-PEG Abs. Various anti-PEG detection methods used in different studies were provided. Several protein modification technologies beyond PEGylation were also highlighted.
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States.
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, United States.
authors.forename: Sijun
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, United States; Department of Bioengineering, University of Washington, Seattle, WA 98195, United States. Electronic address: sjiang@uw.edu.
authors.forename: Shaoyi
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry; D011506:Proteins / Q000737:chemistry
chemical_list: D000906:Antibodies; D011506:Proteins; D011092:Polyethylene Glycols
keywords: Anti-PEG antibody; Antibody detection; Immunogenicity; PEGylation; Polymer conjugation; Protein therapeutics