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The occurrence, induction, specificity and potential effect of antibodies against poly(ethylene glycol)

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PEGylated Protein Drugs: Basic Science and Clinical Applications

Part of the book series: Milestones in Drug Therapy ((MDT))

Abstract

Specific antibodies against poly(ethylene glycol) (anti-PEG) were induced in animals following exposure to PEG-conjugated proteins and particles, resulting in rapid clearance of PEG-conjugated agents. In humans, induction of anti-PEG was observed following exposure to a PEG-conjugated drug, and pre-existing anti-PEG was identified in over 25% the healthy population. In clinical studies, the presence of anti-PEG was strongly associated with rapid clearance of PEG-asparaginase and PEG-uricase. PEGylation of therapeutic agents will continue to be of significant value in medicine to reduce immunogenicity, antigenicity and toxicity as well as markedly reducing renal clearance, while maintaining drug efficacy. It is important to recognize that PEG itself may possess antigenic and immunogenic properties. Further comprehensive studies are warranted to fully elucidate the effect of anti-PEG on PEG-conjugated agents and if confirmed in a prospective trial, patients should be screened and monitored for anti-PEG, and strategies developed to overcome the potential negative effect of anti-PEG on drug clearance to improve the effectiveness of therapy.

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  1. Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, 90033, USA

    Jonathan K. Armstrong

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  1. Department of Pharmaceutical Sciences, University of Padova, 35131, Padova, Italy

    Francesco M. Veronese

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Armstrong, J.K. (2009). The occurrence, induction, specificity and potential effect of antibodies against poly(ethylene glycol). In: Veronese, F.M. (eds) PEGylated Protein Drugs: Basic Science and Clinical Applications. Milestones in Drug Therapy. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8679-5_9

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