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: Masayuki Kai, Kazuhiro Motoki, Hideaki Yoshida, Chie Emuta, Yukiko Chisaka, Kumi Tsuruhata, Chisato Endo, Mari Muto, Munetake Shimabe, Uichi Nishiyama, Tetsuya Hagiwara, Atsushi Matsumoto, Hiroshi Miyazaki, Shiro Kataoka
• Journal: Nature biotechnology (Nat Biotechnol) Vol. 26 Issue 2 Pg. 209-11 (Feb 2008) ISSN: 1546-1696 [Electronic] United States
• PMID: 18157117 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Receptors, Thrombopoietin
• Recombinant Proteins

Topics

• Antibodies, Monoclonal (chemistry, genetics, immunology)
• Genetic Enhancement (methods)
• Protein Engineering (methods)
• Protein Structure, Tertiary
• Receptors, Thrombopoietin (chemistry, genetics, immunology)
• Recombinant Proteins (chemistry, immunology)
• Structure-Activity Relationship