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| Content Provider | PubMed Central |
|---|---|
| Author | Merchant, Mark Ma, Xiaolei Maun, Henry R. Zheng, Zhong Peng, Jing Romero, Mally Huang, Arthur Yang, Nai-ying Nishimura, Merry Greve, Joan Santell, Lydia Zhang, Yu-wen Su, Yanli Kaufman, Dafna W. Billeci, Karen L. Mai, Elaine Moffat, Barbara Lim, Amy Duenas, Eileen T. Phillips, Heidi S. Xiang, Hong Young, Judy C. Woude, George F. Vande Dennis, Mark S. Reilly, Dorothea E. Schwall, Ralph H. Starovasnik, Melissa A. Lazarus, Robert A. Yansura, Daniel G. |
| Abstract | Therapeutic antibodies have revolutionized the treatment of human disease. Despite these advances, antibody bivalency limits their utility against some targets. Here, we describe the development of a one-armed (monovalent) antibody, onartuzumab, targeting the receptor tyrosine kinase MET. While initial screening of bivalent antibodies produced agonists of MET, engineering them into monovalent antibodies produced antagonists instead. We explain the structural basis of the mechanism of action with the crystal structure of onartuzumab antigen-binding fragment in complex with MET and HGF-β. These discoveries have led to an additional antibody-based therapeutic option and shed light on the underpinnings of HGF/MET signaling. |
| Related Links | http://dx.doi.org/10.1073/pnas.1302725110 |
| Starting Page | 2987 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 32 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-08-06 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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