Switching constant domains enhances agonist activities of antibodies to a thrombopoietin receptor.

Kai, Masayuki; Motoki, Kazuhiro; Yoshida, Hideaki; Emuta, Chie; Chisaka, Yukiko; Tsuruhata, Kumi; Endo, Chisato; Muto, Mari et al. · Nat Biotechnol · 2008

basic_science · Level V

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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.

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