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]

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