Anti-PEG antibodies in drug delivery: From origins to mitigation strategies

Poly(ethylene glycol) (PEG) is a cornerstone excipient in drug delivery, widely used to prolong circulation duration and improve the therapeutic efficacy of protein therapeutics and nanomedicines. However, both pre-existing and treatment-induced anti-PEG antibodies have been increasingly recognized during clinical applications, raising concerns regarding the safety, efficacy, and translational reliability of PEGylated therapeutics. In this review, we summarize the origins and prevalence of anti-PEG antibodies, critically evaluate current detection methodologies, and analyze antibody-PEG binding patterns and downstream biological effects, including complement activation, accelerated blood clearance, hypersensitivity reactions, and tissue-specific toxicities, while emphasizing the context-dependent impact of anti-PEG immunity on therapeutic efficacy. We also discuss the emerging strategies to mitigate anti-PEG-mediated risks and outline the key challenges and future directions. This integrated framework aims to facilitate functional interpretation of anti-PEG immunity and support the rational design and clinical translation of next-generation PEGylated drug delivery systems.

Abstract from PubMed (PMID 42966426). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.