title: Relevance of antibody valency in EGF receptor modulation.
abstract: Binding characteristics of a monovalent bispecific monoclonal antibody (bsMoAb), which recognizes both epidermal growth factor receptor (EGF-R) and drug doxorubicin (DXR) were compared with those of the parental bivalent MoAb directed against the EGF-R binding site. Scatchard analysis indicated that both MoAbs bound to EGF-R-overexpressing A431 cells with the same affinity. In tracer amounts, both MoAbs also displayed the same capacity to be internalized after binding to the cell surface. However, when the MoAbs were used at saturating concentrations, down-modulation of the receptor was greater with the bivalent MoAb. The bivalent MoAb also inhibited proliferation of A431 cells both in vitro and in vivo whereas the bsMoAb was inhibitory only in vivo. These data suggest that MoAb bivalency is required for EGF-R down-modulation and in vitro cell growth inhibition.
authors.affiliation: Division of Experimental Oncology E, University of Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Morelli
authors.forename: E
authors.initials: E
authors.lastname: Villa
authors.forename: E
authors.initials: E
authors.lastname: Tagliabue
authors.forename: L
authors.initials: L
authors.lastname: Perletti
authors.forename: M L
authors.initials: ML
authors.lastname: Villa
authors.forename: S
authors.initials: S
authors.lastname: Ménard
authors.forename: A
authors.initials: A
authors.lastname: Balsari
authors.forename: M I
authors.initials: MI
authors.lastname: Colnaghi
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001666:Binding Sites, Antibody; D002455:Cell Division / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D004317:Doxorubicin / Q000276:immunology*; D066246:ErbB Receptors / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D014407:Tumor Cells, Cultured
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D004317:Doxorubicin; D066246:ErbB Receptors