The Benefits of Bispecific mAb-square Antibodies Targeting EGFR and HGF

摘要

F-star's Modular Antibody Technology? platform introduces a novel antigen binding site into the constant (Fc) region of an antibody to create a so-called Fcab? (an Fc-domain with antigen binding activity). The resulting Fcab is then combined with variable region (Fab) of an existing antibody to generate a full-length bispecific antibody or mAb-square?. Here we show how Fcabs targeting Epidermal Growth Factor Receptor (EGFR) are utilised to generate mAb-square molecules that bind specifically EGFR and Hepatocyte Growth Factor (HGF). The EGFR/HGF bispecifics inhibit cell proliferation in vitro and show anti-tumour activity in patient derived xenograft (PDX) models in vivo. The mAb-square molecules show superior inhibition of tumour growth compared to combination treatments in tumours with specific molecular profiles suggesting novel biology of the bispecific.