ANTITUMOR AND CELL-CYCLE RESPONSES IN KB CELLS TREATED WITH A CHIMERIC ANTI-EGFR MONOCLONAL-ANTIBODY IN COMBINATION WITH CISPLATIN

Overexpression of the epidermal growth factor receptor (EGFR) has been found to correlate with a poor prognosis for many cancers. The EGFR a ppears to play an important role in regulating cell growth during tumo rigenesis and blockade of the EGFR/ligand interaction may be a means o f inducing cell cytotoxicity, terminal differentiation, or apoptosis. In this report, we show that the growth of well-established xenografts of the human epidermoid carcinoma cell line KB could be significantly inhibited by the combination of cisplatin plus C225, a chimeric anti- EGFR monoclonal antibody, whereas the individual treatments had no eff ect on tumor growth. Substantive changes in the protein expression lev els of the EGFR as well as several important cell cycle regulatory pro teins were found in cells treated with the combination. In addition, c isplatin plus C225 inhibited the overall phosphorylation patterns incl uding EGFR activation. These in vitro data suggest a mechanism of acti on for the in vivo therapeutic effects of C225 plus cisplatin.