Molecular inhibition of epidermal growth factor receptor (EGFR) function is a promising approach to cancer therapy. In this report, we describe the in vivo activity of a novel, high affinity human anti-EGFR monoclonal antibody, designated IMC-11F8. Antitumor activity of IMC-11F8 was evaluated in models of established (0.20 cm3) epidermoid (A431), pancreatic (BxPC-3) or colon (HT-29 and DLD-1) human tumor xenografts in athymic mice. Dose-dependent inhibition of tumor growth in all models was observed in mice treated with IMC-11F8 (1mg or 0.3mg; 3x/week) with T/C values ranged from 3% to 17% for the 1mg dose and from 38% to 81% for the 0.3mg dose. Histological examination of tumor xenografts demonstrated a significant decrease in the neoplastic cell compartment compared to controls. Combination therapy experiments were performed in colon xenograft models where established DLD-1, GEO, or HT-29 tumors were treated with IMC-11F8, irinotecan (100mg/kg; q7dx5), or the combination. Treatment with combination therapy significantly inhibited the growth of these tumors compared to IMC-11F8 or CPT-11 therapy alone. Combination therapy with the high dose of IMC-11F8 and CPT-11 resulted in synergistic anti-tumor effect in all three tumor models with T/C% values of 8%, 3%, and 10% for DLD-1, GEO and HT-29, respectively. Combination therapy produced tumor regressions in 50% of the DLD-1 and HT-29 animals and in 90% of the GEO tumors. Histological examination of residual tumors after combination treatment showed an increase in pyknotic nuclei and a decrease in mitotic figures; this resulted in a substantial decrease in viable tumor compartment with near elimination of neoplastic cells. The present study shows that IMC-11F8 may be an effective therapy in the treatment of EGFR-positive tumors and warrants clinical evaluation of this agent.
[Proc Amer Assoc Cancer Res, Volume 45, 2004]