title: Switching constant domains enhances agonist activities of antibodies to a thrombopoietin receptor.
abstract: 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.
authors.affiliation: Discovery Research Laboratories, Kirin Pharma Co., Ltd., 3 Miyahara, Takasaki, Gunma, 370-1295, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Motoki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Chie
authors.initials: C
authors.lastname: Emuta
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Chisaka
authors.forename: Kumi
authors.initials: K
authors.lastname: Tsuruhata
authors.forename: Chisato
authors.initials: C
authors.lastname: Endo
authors.forename: Mari
authors.initials: M
authors.lastname: Muto
authors.forename: Munetake
authors.initials: M
authors.lastname: Shimabe
authors.forename: Uichi
authors.initials: U
authors.lastname: Nishiyama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hagiwara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Shiro
authors.initials: S
authors.lastname: Kataoka
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins