INHIBITORY EFFECT OF ANTIEPIDERMAL GROWTH-FACTOR RECEPTOR ANTIBODY ONA HUMAN GASTRIC-CANCER

BACKGROUND. Blockading the putative epidermal growth factor (EGF), tra nsforming growth factor-alpha (TGF-alpha)/EGF receptor autocrine pathw ay with anti-EGF receptor monoclonal antibody (MoAb) might prevent the growth of tumor. METHODS. The present study was designed to examine t he effect of MoAb 528 on the growth of an EGF receptor which was hyper producing human gastric cancer cells in vitro and in vivo. RESULTS. Tr eatment with MoAb 528 inhibited the growth of cultured cells in a dose -dependent manner. Twenty micrograms of MoAb 528 given intraperitoneal ly after inoculation of 1 x 10(6) cells and 200 mu g of the MoAb given after inoculation of 1 x 10(7) cells to athymic mice inhibited the gr owth of the xenograft. Twenty micrograms of MoAb 528 from a miniosmoti c pump, which releases its contents over 2 weeks, also prevented the g rowth of the xenograft when the treatment was started on the day after turner inoculation. However, no inhibitory effect was observed when t he treatment was started 3 weeks after inoculation. The binding capaci ty of I-125-EGF on the MoAb treated tumors was diminished in compariso n with control tumors. CONCLUSIONS. The results suggest that MoAb 528 blocks the EGF or TGF-alpha/EGF receptor signal pathway, resulting in the inhibition of cancer cell growth. This MoAb 528 may therefore be a n effective antitumor agent against human gastric cancer that shows ex pression of the EGF receptor. (C) 1996 American Cancer Society.