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MetMAb

Blocking HGF/SF binding may prevent Met dimerization and activation, ultimately inhibiting downstream signaling events.1,2

GA101
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Onartuzumab (MetMAb) is a monovalent (one-armed), monoclonal antibody designed to bind to Met and inhibit HGF/SF binding.3,4 Traditional bivalent antibodies to Met potentially activate, rather than inhibit, Met signaling by inducing Met dimerization.5-6 In contrast, the monovalent design of Onartuzumab (MetMAb) inhibits HGF/SF binding without inducing Met dimerization.4 Onartuzumab (MetMAb) has demonstrated antitumor activity in preclinical analyses.4

  1. MetMAb was specifically designed as a monovalent antibody to avoid agonistic activity that may occur when a bivalent antibody binds two Met molecules.4,6

    MetMAb Vignette 1

  2. MetMAb binds to the Sema domain of Met, an extracellular region essential for binding its ligand, HGF/SF.3,4

    MetMAb Vignette 2

  3. MetMAb inhibits HGF/SF from binding to Met, thereby blocking ligand-induced Met dimerization and activation of the intracellular kinase domain.4

    MetMAb Vignette 3

  4. Blockade of Met activation inhibits its downstream pathways, preventing cancer cell growth, survival, and metastasis.4

    MetMAb Vignette 4

References:
1.
Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. Met, metastasis, motility and more. Nat Rev Mol Cell Biol. 2003;4:915-925. PMID: 14685170
2.
Abounader R, Laterra J. Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro Oncol. 2005;7:436-451. PMID: 16212809
3.
Kong-Beltran M, Stamos J, Wickramasinghe D. The Sema domain of Met is necessary for receptor dimerization and activation. Cancer Cell. 2004;6:75-84. PMID: 15261143
4.
Martens T, Schmidt NO, Eckerich C, et al. A novel one-armed anti-c-Met antibody inhibits glioblastoma growth in vivo. Clin Cancer Res. 2006;12:6144-6152. PMID: 17062691
5.
Ohashi K, Marion PL, Nakai H, et al. Sustained survival of human hepatocytes in mice: A model for in vivo infection with human hepatitis B and hepatitis delta viruses. Nat Med. 2000;6:327-331. PMID: 10700236
6.
Prat M, Crepaldi T, Pennacchietti S, Bussolino F, Comoglio PM. Agonistic monoclonal antibodies against the Met receptor dissect the biological responses to HGF. J Cell Sci. 1998;111:237-247. PMID: 9405310