Identification and characterization of a fully human antibody directed against epidermal growth factor receptor for cancer therapy

706 Epidermal growth factor receptor (EGFR) has been implicated in promoting oncogenesis and progression of many human tumors, and is expressed in a variety of human solid tumors including carcinomas of head and neck, lung, colorectum, pancreas, prostate, and kidney. We have previously demonstrated that a chimeric anti-EGFR antibody, ErbituxTM (cetuximab), was an efficacious agent in inhibiting the growth of a variety of human xenograft tumors in animal models. In this study, we produced a fully human antibody directed against EGFR, IMC-11F8 (IgG1), from a Fab fragment originally identified from a naive phage display library. IMC-11F8 binds to EGFR with an affinity of ∼ 0.28 nM, and effectively blocks EGF-stimulated receptor phosphorylation and activation of MAP kinases in a number of tumor cell lines. The antibody also inhibits the in vitro growth of several EGFR-overexpressing tumor cell lines including DiFi (colorectal), A431 (epidermal) and BxPC3 (pancreatic). Taken together, these results suggest that IMC-11F8 may have great clinical potential in the treatment of EGFR+ human cancers.