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] Related Links PEGylation of anti-sialoadhesin monoclonal antibodies enhances their inhibitory potencies without impairing endocytosis in mouse peritoneal macrophages. [Bioconjug Chem. 2009] PMID:19143515 Sialoadhesin on macrophages: its identification as a lymphocyte adhesion molecule. [J Exp Med. 1992] PMID:1512534 Macrophage-tumour cell interactions: identification of MUC1 on breast cancer cells as a potential counter-receptor for the macrophage-restricted receptor, sialoadhesin. [Immunology. 1999] PMID:10610356 PEGylation and multimerization of the anti-p185HER-2 single chain Fv fragment 4D5: effects on tumor targeting. [J Biol Chem. 2006] PMID:16963450 Cutting edge: CD43 functions as a T cell counterreceptor for the macrophage adhesion receptor sialoadhesin (Siglec-1). [J Immunol. 2001] PMID:11238599