Epidermal growth factor receptor blockade by antibody IMC-C225 inhibits growth of a human pancreatic carcinoma xenograft in nude mice

BACKGROUND. Pancreatic carcinoma is associated with a poor prognosis, and t reatment options for patients with this disease are limited. The epidermal growth factor (EGF) receptor and its ligands are overexpressed in human pan creatic carcinoma and may contribute to the pathophysiology of these tumors . METHODS. The anti-EGF receptor monoclonal antibody IMC-C225 was used to det ermine the effects of EGF receptor blockade on the growth of human pancreat ic carcinoma BxPC-3 cells in vitro. Athymic mice bearing established (200 m m(3)) subcutaneous BxPC-3 xenografts were treated with IMC-C225 (17 or 33 m g/kg every 3 days) alone or in combination with 5-fluorouracil (17 mg/kg tw ice weekly). RESULTS. IMC-C225 inhibited exogenous ligand-stimulated tyrosine phosphoryl ation of the EGF receptor on BxPC-3 tumor cells. Treatment of BxPC-3 cells with IMC-C225 inhibited DNA synthesis (23.8%) and colony formation in soft agar (45.6%). IMC-C225 treatment significantly suppressed the growth of BxP C-3 tumors compared with treatment with vehicle alone (P = 0.003). Combinat ion therapy with IMC-C225 and the chemotherapeutic agent 5-fluorouracil enh anced the antitumor effects compared with either agent alone and resulted i n regression of pancreatic tumors in several animals. Histologic examinatio n of pancreatic tumors from mice treated with IMC-C225 showed extensive tum or necrosis that coincided with a substantial decrease in tumor cell prolif eration and an increase in tumor cell apoptosis. CONCLUSIONS. These data suggest that IMC-C225 affects the growth of pancrea tic tumors by inhibiting EGF receptor-dependent proliferation and survival, and demonstrates the potential for therapeutic application of IMC-C225 ant ibody in the treatment of human pancreatic carcinoma. (C) 2000 American Can cer Society.