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The Immunogenicity of Polyethylene Glycol: Facts and Fiction

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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.

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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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Authors and Affiliations

  1. Department of Pharmaceutics Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands

    Huub Schellekens, Wim E. Hennink & Vera Brinks

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  1. Huub Schellekens
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  2. Wim E. Hennink
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  3. Vera Brinks
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Correspondence to Vera Brinks.

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Schellekens, H., Hennink, W.E. & Brinks, V. The Immunogenicity of Polyethylene Glycol: Facts and Fiction. Pharm Res 30, 1729–1734 (2013). https://doi.org/10.1007/s11095-013-1067-7

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  • DOI: https://doi.org/10.1007/s11095-013-1067-7

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