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 naïve 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.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]