Anti-Human c-MET Monoclonal Antibody (Emibetuzumab)

c-MET, also known as hepatocyte growth factor receptor (HGFR), is a receptor tyrosine kinase encoded by the MET proto-oncogene and belongs to the transmembrane receptor family. Its natural ligand is hepatocyte growth factor (HGF). Structurally, the protein consists of an extracellular SEMA domain (responsible for ligand binding), a PSI domain, and IPT repeats (involved in receptor dimerization and signal transduction), followed by a transmembrane region, as well as an intracellular juxtamembrane domain and a tyrosine kinase domain. Upon HGF binding to the extracellular domain of c-MET, the receptor undergoes dimerization and transphosphorylation at specific intracellular tyrosine residues (e.g., Y1234 and Y1235), thereby activating multiple downstream signaling pathways, including RAS-MAPK, PI3K-AKT, STAT3, and Wnt/β-catenin. These pathways play core regulatory roles in physiological processes such as embryonic development (particularly in the liver, placenta, and nervous system), tissue regeneration, and wound healing. Aberrant activation of c-MET signaling is extremely common in human cancers, primarily driven by MET gene amplification, mutations, overexpression, or paracrine/autocrine loops of its ligand HGF. This dysregulation is observed in a variety of solid tumors, including non-small cell lung cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, and glioblastoma, where it promotes tumor cell proliferation, epithelial-mesenchymal transition, invasion, metastasis, and angiogenesis, while also contributing to chemotherapy resistance and targeted therapy resistance. In recent years, small-molecule c-MET inhibitors such as crizotinib, capmatinib, and tepotinib, as well as anti-c-MET monoclonal antibodies (e.g., emibetuzumab), have demonstrated significant clinical efficacy in indications such as non-small cell lung cancer with MET exon 14 skipping mutations, establishing c-MET as a critical molecular typing biomarker and drug intervention target in precision oncology.