[Research] 2021/09/11

Polyethylene Glycol Immunogenicity: Theoretical, Clinical, and Practical Aspects of Anti-Polyethylene Glycol Antibodies


A team led by Dr. Steve Roffler at the Institute of Biomedical Sciences (IBMS) in Academia Sinica published a review and perspective of polyethylene glycol immunogenicity in the journal ACS Nano on September 1st, 2021.

Attachment of polyethylene glycol (PEG) to small molecules, nucleotides, peptides, proteins, liposomes and nanoparticles is widely used to improve their stability, solubility and pharmacokinetic properties. Prolonged circulation times enhances patient compliance and quality of life because the frequency of needle injections can be dramatically reduced. Due to the beneficial properties of PEG, nearly thirty pegylated protein and non-protein medicines are already clinically available including BNT/Pfizer and Moderna RNA vaccines against SARS-CoV-2. However, administration of some pegylated medicines causes generation of antibodies that bind to PEG. These antibodies can accelerate the clearance of PEG drugs from the circulation, activate complement to cause premature drug release from liposomal drugs and induce hypersensitivity reactions that can be life-threatening. Many normal individuals also have pre-existing antibodies against PEG in their circulation, likely due to the widespread use of PEG in many cosmetic and healthcare products, which may also impact drug efficacy and safety.

        A clear understanding of when and how anti-PEG antibodies impact drug efficacy and safety is needed for a realistic assessment of one of the most widely used and successful polymers in drug delivery. Based on literature precedents and over twenty-year experience developing and investigating antibodies that bind to PEG, we provide a framework to understand what makes a pegylated drugs immunogenic, how anti-PEG antibodies affect the efficacy and safety of pegylated medicines, and our experience with how anti-PEG antibodies behave in practice.

Dr. Steve Roffler said, “We hope that this publication can clear up some misconceptions about PEG immunogenicity, help medical personnel assess the impact of anti-PEG antibodies on pegylated drugs, and help create more effective and safe medicines. Widespread use of SARS-CoV-2 RNA vaccines raise new questions because these vaccines incorporate PEG in their lipid nanoparticles and may induce antibodies against PEG in many individuals. It is critical that physicians are made aware that the safety and efficacy of previously safe pegylated medicines may change as RNA vaccines are increasingly used. More testing for anti-PEG antibodies before administration of pegylated drugs may be warranted in the near future.”

This work was supported by intramural funding from Academia Sinica and a grant from the Ministry of Science and Technology. The full article entitled “Polyethylene Glycol Immunogenicity: Theoretical, Clinical, and Practical Aspects of Anti-Polyethylene Glycol Antibodies” can be found at the ACS Nano website at: https://pubs.acs.org/doi/abs/10.1021/acsnano.1c05922. The complete list of authors is: Bing-Mae Chen, Tian-Lu Cheng and Steve R. Roffler.

Article link (ACS Nano)