1: Bioconjug Chem. 2008 Oct;19(10):2088-94. Epub 2008 Sep 23.

The inhibitory potencies of monoclonal antibodies to the macrophage adhesion
molecule sialoadhesin are greatly increased following PEGylation.

Ducreux J, Vanbever R, Crocker PR.

Department of Pharmaceutical Technology, School of Pharmacy, Université
Catholique de Louvain, 1200 Brussels, Belgium.

PEGylation of antibodies is known to increase their half-life in systemic
circulation, but nothing is known regarding whether PEGylation can improve the
inhibitory potency of antibodies against target receptors. In this paper, we have
examined this question using antibodies directed to Sialoadhesin (Sn), a
macrophage-restricted adhesion molecule that mediates sialic acid dependent
binding to different cells. Anti-Sn monoclonal antibodies (mAbs), SER-4 and 3D6, 
were conjugated to PEG 5 kDa or and PEG 20 kDa, resulting in the incorporation of
up to 3 molecules of PEG per mAb molecule. Following purification of PEGylated
mAbs by anion exchange chromatography, it was shown that PEGylation had little or
no effect on antigen binding activity but led to a dramatic increase in
inhibitory potency that was proportional to both the size of the PEG and the
degree of derivatization. Thus, PEGylation of antibodies directed to cell surface
receptors could be a powerful approach to improve the therapeutic efficacy of
antibodies, not only by increasing their half-life in vivo, but also by
increasing their inhibitory potency for blocking receptor-ligand interactions.


PMID: 18808170 [PubMed - indexed for MEDLINE]

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