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Details on Person Recombinant monoclonal anti-MET therapeutic antibodies are e...

Class:IdSummation:9734142
_displayNameRecombinant monoclonal anti-MET therapeutic antibodies are e...
_timestamp2021-07-06 14:07:16
created[InstanceEdit:9734140] Orlic-Milacic, Marija, 2021-06-15
literatureReference[LiteratureReference:9734090] Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent
[LiteratureReference:9734111] LY2875358, a neutralizing and internalizing anti-MET bivalent antibody, inhibits HGF-dependent and HGF-independent MET activation and tumor growth
[LiteratureReference:9734120] Depleting MET-Expressing Tumor Cells by ADCC Provides a Therapeutic Advantage over Inhibiting HGF/MET Signaling
[LiteratureReference:8875387] Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody
[LiteratureReference:9734106] Met degradation by SAIT301, a Met monoclonal antibody, reduces the invasion and migration of nasopharyngeal cancer cells via inhibition of EGR-1 expression
[LiteratureReference:9734139] Known and novel roles of the MET oncogene in cancer: a coherent approach to targeted therapy
modified[InstanceEdit:9736294] Orlic-Milacic, Marija, 2021-07-06
textRecombinant 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).
(summation)[Reaction:9734070] Anti-MET recombinant therapeutic antibodies bind MET [Homo sapiens]
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