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

ABSTRACT:

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 we

SUBMITTER: Wang J 

PROVIDER: S-EPMC4755020 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature