Targeting EGFR/HER2 heterodimerization with a novel anti-HER2 domain II/III antibody. (July 2017)

• Record Type: Journal Article
• Authors: Yu, Xiaojie; Wang, Lingfei; Shen, Yafeng; Wang, Chao; Zhang, Yajun; Meng, Yanchun; Yang, Yang; Liang, Beibei; Zhou, Bo; Wang, Huajing; Wei, Huafeng; Lei, Changhai; Hu, Shi; Li, Bohua
• Is Part Of: Molecular immunology. Volume 87(2017:Jul.)
• Page Start: 300
• Page End: 307
• Publication Date: 2017-07
• Subjects: Breast cancer -- HER2 -- Transmembrane signal transduction -- Structural analysis; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2017.05.010
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: A novel anti-HER2 antibody was developed. There was a structural conformation change in HER2 in complex with 7C3. The antibody could block HER2/EGFR heterodimerization and signaling. It reveals a unique potential to complement current anti-HER2 treatment strategy. Abstract: HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. Despite the effectiveness of trastuzumab, its efficacy remains variable and often modest. Thus, there is an urgent need to improve ErbB2-targeting therapy. Here, we describe a novel anti-HER2 antibody, 7C3, which was developed using hybridoma technique. Structural analysis confirms that the epitope of this antibody is in domain II/III of HER2. Moreover, a structural conformation change was observed in HER2 in complex with 7C3. Interestingly, this novel anti-HER2 antibody exhibits efficacy in blocking HER2/EGFR heterodimerization and signaling. The results highlight the different function role of HER2 domains and the unique potential of 7C3 to inhibit the HER2/EGFR heterodimer, which may complement current anti-HER2 treatments.