Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity.
Four mouse monoclonal antibodies specific for human epidermal growth factor (EGF) receptors have been prepared using EGF receptor protein from human A431 epidermoid carcinoma cells as immunogen. We have determined the effect of these antibodies on two known functions of the EGF receptor: EGF binding and tyrosine kinase. Three of these antibodies (225, 528, and 579) are inhibitors of EGF binding, whereas the fourth (455) does not compete for binding but immunoprecipitates the EGF receptor. Inhibition is of the mixed competitive and noncompetitive type. The three competing monoclonal antibodies are antagonists of EGF-stimulated tyrosine protein kinase activity assayed both in intact cells and using an exogenous peptide substrate in solubilized membranes. These immunoglobulins are partial agonists in self-phosphorylation of the EGF receptor in solubilized membranes but exhibit only antagonist activity for this reaction in intact cells. The three competing monoclonal immunoglobulins recognize receptors in variant A431 cells with the same efficiency as in parental A431 cells. Such antagonist monoclonal antibodies can be used to control the concentration of receptors which can be activated by EGF.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D047428:Protein Kinase Inhibitors; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases