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Background  c-Met is the receptor tyrosine kinase for hepatocyte growth factor (HGF) encoded by the  MET  proto-oncogene. Aberrant activation of c-Met resulting from  MET  amplification and c-Met overexpression is associated with poor clinical outcome in multiple malignancies underscoring the importance of c-Met signaling in cancer progression. Several c-Met inhibitors have advanced to the clinic; however, the development of inhibitory c-Met-directed therapeutic antibodies has been hampered by inherent agonistic activity.    Method  We generated and tested a bivalent anti-c-Met monoclonal antibody ABT-700 in vitro for binding potency and antagonistic activity and in vivo for antitumor efficacy in human tumor xenografts. Human cancer cell lines and gastric cancer tissue microarrays were examined for MET amplification by fluorescence in situ hybridization (FISH).    Results  ABT-700 exhibits a distinctive ability to block both HGF-independent constitutive c-Met signaling and HGF-dependent activation of c-Met. Cancer cells addicted to the constitutively activated c-Met signaling driven by  MET  amplification undergo apoptosis upon exposure to ABT-700. ABT-700 induces tumor regression and tumor growth delay in preclinical tumor models of gastric and lung cancers harboring amplified  MET . ABT-700 in combination with chemotherapeutics also shows additive antitumor effect. Amplification of  MET  in human cancer tissues can be identified by FISH.    Conclusions  The preclinical attributes of ABT-700 in blocking c-Met signaling, inducing apoptosis and suppressing tumor growth in cancers with amplified  MET  provide rationale for examining its potential clinical utility for the treatment of cancers harboring  MET  amplification.    Electronic supplementary material  The online version of this article (doi:10.1186/s12885-016-2138-z) contains supplementary material, which is available to authorized users.

Anti-c-Met monoclonal antibody ABT-700 breaks oncogene addiction in tumors with MET amplification