Reactome | Anti-MET recombinant therapeutic antibodies bind MET

Anti-MET recombinant therapeutic antibodies bind MET

Stable Identifier

R-HSA-9734070

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane

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Anti-MET recombinant therapeutic antibodies bind MET

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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