c-Met is a Potential Therapeutic Target for Antibody Drug Conjugates in Breast Cancer

Click on the text to edit) c-Met, a transmembrane receptor tyrosine kinase, plays a key role in malignant transformation of epithelial cells by activating signal transduction pathways essential for cellular proliferation, survival, migration and invasion. c-Met overexpression, with or without gene amplification, has been reported in primary breast cancers and correlated with poor prognosis. c-Met signaling inhibition, such as tyrosine kinase inhibitors (TKIs), are usually not sufficient for sustained treatment efficacy. We believe that antibody drug conjugates (ADCs) offer the promise and potential of delivering potent anti tumor activity with the advantage of reduced side effects. We generated antibody drug conjugates containing a proprietary human anti-c-Met antibody (STI-0602) with either a tubulin inhibitor or DNA damaging agent, such as doxorubicin analogs. STI-0602, a fully human antibody (IgG1) selected from phage library was conjugated with the cytotoxin via site-specific bioconjugation. The conjugates retained binding affinity and showed potent cell killing in a variety of c-Met-positive cell lines. Progress will be reported in terms of in vivo efficacy in c-Met-positive human breast tumor xenograft in preclinical models.