Potential induction of anti-PEG antibodies and complement activation toward PEGylated therapeutics.

Autor: Verhoef JJ; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands. Electronic address: j.j.f.verhoef@uu.nl., Carpenter JF; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, USA., Anchordoquy TJ; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, USA., Schellekens H; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: Drug discovery today [Drug Discov Today] 2014 Dec; Vol. 19 (12), pp. 1945-52. Date of Electronic Publication: 2014 Sep 07.
DOI: 10.1016/j.drudis.2014.08.015
Abstrakt: Conjugation of polyethylene glycol (PEG) to therapeutics has proven to be an effective approach to increase the serum half-life. However, the increased use of PEGylated therapeutics has resulted in unexpected immune-mediated side-effects. There are claims that these are caused by anti-PEG antibodies inducing rapid clearance. These claims are however hampered by the lack of standardized and well-validated antibody assays. PEGylation has also been associated with the activation of the complement system causing severe hypersensitivity reactions. Here, we critically review the clinical and analytical tools used. In addition, we propose an explanation of the immune-mediated side-effects of PEGylated products based on the haptogenic properties of PEG, responsible for complement activation and the induction of anti-PEG antibodies.
(Copyright © 2014 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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