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Pharmaceutical Research

, Volume 30, Issue 7, pp 1729–1734 | Cite as

The Immunogenicity of Polyethylene Glycol: Facts and Fiction

  • Huub Schellekens
  • Wim E. Hennink
  • Vera BrinksEmail author
Expert Review

ABSTRACT

An increasing number of pegylated therapeutic proteins and drug targeting compounds are being introduced in the clinic. Pegylation is intended to increase circulation time and to reduce an immunogenic response. Recently however a number of publications have appeared claiming that the polyethylene glycol (PEG) moiety of these products in itself may be immunogenic and that the induced anti-PEG antibodies are linked to enhanced blood clearance and reduced efficacy of the products. A critical review of the literature shows that most, if not all assays for anti-PEG antibodies are flawed and lack specificity. Also the biological effects induced by anti-PEG antibodies lack the characteristics of a bona fide antibody reaction. Standardization of the anti-PEG assays and the development of reference sera are urgently needed.

KEY WORDS

immune assays immunogenicity pegylation therapeutic proteins 

ABBREVIATIONS

ABC

Accelerated blood clearance

BSA

Bovine serum albumin

ELISA

Enzyme linked immunosorbent assay

EMA

European medicines agency

FDA

Food and drug administration

Ig

Immunoglobulin

OVA

Ovalbumin

pDNA

Plasmid DNA

PEG

Polyethylene glycol

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Huub Schellekens
    • 1
  • Wim E. Hennink
    • 1
  • Vera Brinks
    • 1
    Email author
  1. 1.Department of Pharmaceutics Utrecht Institute of Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands

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