Conclusion
The one-armed anti-c-Met antibody derived from the full-length bivalent anti-c-Met antibody might serve as a potential antitumor agent against HCC.
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 anti-c-Met antibody. In addition, the antibody also reduced the HGF-induced proliferation and tube formation of human umbilical vein endothelial cells (HUVECs). Treating HepG2-bearing mice with the one-armed anti-c-Met antibody significantly inhibited the tumor growth in the xenograft nude mouse model.