抗体
抗原
单克隆抗体
结合位点
分子生物学
血管内皮生长因子
化学
生物
细胞生物学
癌症研究
生物化学
血管内皮生长因子受体
免疫学
作者
Jenny Boström,Shang‐Fan Yu,David Kan,B.A. Appleton,Chingwei V. Lee,Karen L. Billeci,Wenyan Man,Franklin Peale,Sarajane Ross,Christian Wiesmann,Germaine Fuh
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2009-03-20
卷期号:323 (5921): 1610-1614
被引量:327
标识
DOI:10.1126/science.1165480
摘要
The interface between antibody and antigen is often depicted as a lock and key, suggesting that an antibody surface can accommodate only one antigen. Here, we describe an antibody with an antigen binding site that binds two distinct proteins with high affinity. We isolated a variant of Herceptin, a therapeutic monoclonal antibody that binds the human epidermal growth factor receptor 2 (HER2), on the basis of its ability to simultaneously interact with vascular endothelial growth factor (VEGF). Crystallographic and mutagenesis studies revealed that distinct amino acids of this antibody, called bH1, engage HER2 and VEGF energetically, but there is extensive overlap between the antibody surface areas contacting the two antigens. An affinity-improved version of bH1 inhibits both HER2- and VEGF-mediated cell proliferation in vitro and tumor progression in mouse models. Such "two-in-one" antibodies challenge the monoclonal antibody paradigm of one binding site, one antigen. They could also provide new opportunities for antibody-based therapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI