1: Bioconjug Chem. 2009 Feb;20(2):295-303. PEGylation of anti-sialoadhesin monoclonal antibodies enhances their inhibitory potencies without impairing endocytosis in mouse peritoneal macrophages. Ducreux J, Tyteca D, Ucakar B, Medts T, Crocker PR, Courtoy PJ, Vanbever R. Department of Pharmaceutical Technology, School of Pharmacy, de Duve Institute, Universite Catholique de Louvain, 1200 Brussels, Belgium. Poly(ethylene glycol) (PEG) 5 kDa and 20 kDa have been previously conjugated to two anti-sialoadhesin (Sn) monoclonal antibodies (mAbs), SER-4 and 3D6, and shown to dramatically increase their inhibitory potency in solid-phase red blood cell binding assays. In the present study, we evaluated the effect of anti-Sn SER-4 and 3D6 mAbs PEGylation on their inhibition of cell adhesion in mouse peritoneal macrophages. We also examined whether Sn-mediated PEGylation could affect plasma membrane functions of macrophages as to prevent accessibility, binding, and endocytosis of macromolecules and particles. Conjugation of PEG to plasma membrane is known to cause immune tolerance by impairing protein-protein and cell-cell interactions. PEGylation of SER-4 and 3D6 mAbs increased by 4-fold their inhibition of Sn-mediated erythrocyte binding to macrophages. PEGylated SER-4 and 3D6 mAbs did not impair macrophage membrane integrity, cell metabolism, nor pinocytosis of macromolecules and phagocytosis of latex particles. Thus, PEGylation of antibodies directed to cell surface receptors could be potentially exploited in a therapeutic setting to increase inhibitory potency of antibodies without impairing vital functions of cells. PMID: 19143515 [PubMed - in process] Related Links The inhibitory potencies of monoclonal antibodies to the macrophage adhesion molecule sialoadhesin are greatly increased following PEGylation. [Bioconjug Chem. 2008] PMID:18808170 Monocyte/macrophage interactions with base and linear- and star-like PEG-modified PEG-poly(acrylic acid) co-polymers. [J Biomed Mater Res A. 2003] PMID:12833432 Characterization of site-specific ScFv PEGylation for tumor-targeting pharmaceuticals. [Bioconjug Chem. 2005] PMID:15656582 Effect of phagocytosis on receptor distribution and endocytic activity in macrophages. [J Cell Physiol. 1987] PMID:3036889 Sialoadhesin expression by bone marrow macrophages derived from Ehrlich-tumor-bearing mice. [Cancer Immunol Immunother. 1999] PMID:10602886