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Yanxin Yin,1,2,* Jia Guo,1,2,* Fei Teng,1,2 Lihua Yu,2 Yun Jiang,2 Kun Xie,3 Ming Jiang,1,2 Jianmin Fang1–3 1Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, People’s Republic of China; 2Biomedical Research Center, Tongji University Suzhou Institute, Suzhou, Jiangsu 215101, People’s Republic of China; 3School of Life Science and Technology, Tongji University, Shanghai 200092, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming JiangBiomedical Research Center, Tongji University Suzhou Institute, Building 2,198 Jinfeng Road, Wuzhong District, Suzhou, Jiangsu 215101, People’s Republic of ChinaTel +86 512 6601 6586Email jiangm@tongji.edu.cn Jianmin FangSchool of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, People’s Republic of ChinaTel +86 21 6598 2878Email jfang@tongji.edu.cnIntroduction: Antibody-based c-mesenchymal–epithelial transition factor (c-Met) inhibition is a promising strategy for hepatocellular carcinoma (HCC) treatment, but the intrinsic agonistic activity of the anti-c-Met antibody limits its application in drug development. Constructing a monovalent one-armed antibody has been reported to be an effective way to create an inhibitory anti-c-Met antibody.Materials and methods: In the present study, a novel monovalent one-armed anti-c-Met antibody was constructed using the knobs-into-holes technology, and its inhibitory effects against HCC and the underlying mechanisms were explored.Results: The one-armed anti-c-Met antibody blocked the hepatocyte growth factor (HGF)/c-Met interaction and the subsequent signal transduction, including phosphorylation of c-Met, Grb2-associated binding protein 1(Gab-1), extracellular regulated protein kinases 1/2(Erk1/2), and Akt, also referred to as protein kinase B (PKB) in HCC cell line HepG2. Furthermore, the autocrine stimulation of HepG2 cell proliferation and HGF-induced HCC cell migration were strongly inhibited by the one-armed ... |