Development of a MET-targeted single-chain antibody fragment as an anti-oncogene targeted therapy for breast cancer

Abstract

Abstract The usage of monoclonal antibodies (mAbs), as a matter associated with the biopharmaceutical industry, is increasingly growing. Harmonious with this concept, we designed the exquisitely modeled anti-MET scFv against breast cancer by gene cloning, and expression using a bacterial host. Herein, we developed a recombinant scFv against MET and examined its preclinical efficacy for the reduction of tumor growth, invasiveness and angiogenesis in vitro and in vivo. Expressed anti-MET scFv demonstrated high binding capacity (48.8%) toward MET-overexpressing cancer cells. The IC50 value of anti-MET scFv against MET-positive human breast cancer cell line (MDA-MB-435) was 11.4 nM whereas this value was measured as 47.01 nM in MET-negative cell line BT-483. Similar concentrations could also effectively induce apoptosis in MDA-MB-435 cancer cells. Moreover, this antibody fragment could reduce migration and invasion in MDA-MB-435 cells. Grafted breast tumors in Balb/c mice showed significant tumor growth suppression as well as reduction of blood-supply in response to recombinant anti-MET treatment. Histopathology and immunohistochemical assessments revealed higher rate of response to therapy. In our study, we designed and synthetized a novel anti-MET scFv which could effectively suppress MET-overexpressing breast cancer tumors.