Anti-MET recombinant therapeutic antibodies bind MET

Stable Identifier
R-HSA-9734070
Type
Reaction [binding]
Species
Homo sapiens
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Recombinant monoclonal anti-MET therapeutic antibodies are emerging as promising targeted therapeutics for the treatment of MET-driven cancers (reviewed in Comoglio et al. 2018).

Onartuzumab (also known as MetMAb), is an E. coli-derived humanized monovalent (one-armed) antibody that binds to MET and inhibits binding of HGF alpha chain to MET, thus preventing HGF-mediated activation of MET signaling. Onartuzumab does not display HGF agonism which is characteristic of some bivalent MET antibodies (Merchant et al. 2013).

Emibetuzumab (also known as LY2875358) is a humanized bivalent anti-MET monoclonal antibody which inhibits binding of HGF to MET and prevents HGF-mediate MET activation without exhibiting HGF agonism. In addition, emibetuzumab induces MET internalization and degradation, which further interferes with MET signaling (Liu et al. 2014).

ARGX-111 is an engineered anti-MET monoclonal antibody which competes with HGF for MET binding, acting as an HGF antagonist, inhibits HGF-induced MET activation, and engages natural killer cells to kill MET-expressing cancer cells, exhibiting enhanced antibody-dependent cellular toxicity (Hultberg et al. 2015).

SAIT301 is a bivalent recombinant anti-MET monoclonal antibody that likely acts as an HGF antagonist, but detailed studies are lacking. SAIT301 is thus annotated as a candidate HGF antagonist. SAIT301 inhibits activation of MET signaling by HGF and induces MET degradation that is independent of the MET E3 ubiquitin ligase CBL (Lee, Kim et al. 2014; Lee, Kang et al. 2014).

Literature References
PubMed ID Title Journal Year
23882082 Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent

Merchant, M, Ma, X, Maun, HR, Zheng, Z, Peng, J, Romero, M, Huang, A, Yang, NY, Nishimura, M, Greve, J, Santell, L, Zhang, YW, Su, Y, Kaufman, DW, Billeci, KL, Mai, E, Moffat, B, Lim, A, Duenas, ET, Phillips, HS, Xiang, H, Young, JC, Vande Woude, GF, Dennis, MS, Reilly, DE, Schwall, RH, Starovasnik, MA, Lazarus, RA, Yansura, DG

Proc Natl Acad Sci U S A 2013
24722284 Met degradation by SAIT301, a Met monoclonal antibody, reduces the invasion and migration of nasopharyngeal cancer cells via inhibition of EGR-1 expression

Lee, BS, Kang, S, Kim, KA, Song, YJ, Cheong, KH, Cha, HY, Kim, CH

Cell Death Dis 2014
23208509 Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody

Lee, JM, Kim, B, Lee, SB, Jeong, Y, Oh, YM, Song, YJ, Jung, S, Choi, J, Lee, S, Cheong, KH, Kim, DU, Park, HW, Han, YK, Kim, GW, Choi, H, Song, PH, Kim, KA

Oncogene 2014
26141862 Depleting MET-Expressing Tumor Cells by ADCC Provides a Therapeutic Advantage over Inhibiting HGF/MET Signaling

Hultberg, A, Morello, V, Huyghe, L, De Jonge, N, Blanchetot, C, Hanssens, V, De Boeck, G, Silence, K, Festjens, E, Heukers, R, Roux, B, Lamballe, F, Ginestier, C, Charafe-Jauffret, E, Maina, F, Brouckaert, P, Saunders, M, Thibault, A, Dreier, T, de Haard, H, Michieli, P

Cancer Res 2015
25231402 LY2875358, a neutralizing and internalizing anti-MET bivalent antibody, inhibits HGF-dependent and HGF-independent MET activation and tumor growth

Liu, L, Zeng, W, Wortinger, MA, Yan, SB, Cornwell, P, Peek, VL, Stephens, JR, Tetreault, JW, Xia, J, Manro, JR, Credille, KM, Ballard, DW, Brown-Augsburger, P, Wacheck, V, Chow, CK, Huang, L, Wang, Y, Denning, I, Davies, J, Tang, Y, Vaillancourt, P, Lu, J

Clin Cancer Res 2014
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