Switching constant domains enhances agonist activities of antibodies to a thrombopoietin receptor.
We enhanced the activities of two agonist antibodies specific for the thrombopoietin receptor (c-MPL) by switching domains within their constant regions to those of different antibody isotypes. Our results suggest the importance of the hinge region in modulating agonist activity. The antibodies' thrombopoietin-like activity in vitro and in vivo, as well as the desirable pharmacokinetic profile conferred by retaining the whole-IgG structure, suggests that they provide a valuable option for treating thrombocytopenia.
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D024861:Genetic Enhancement / Q000379:methods*; D015202:Protein Engineering / Q000379:methods*; D017434:Protein Structure, Tertiary; D053628:Receptors, Thrombopoietin / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins