ANTITUMOR-ACTIVITY OF ANTIEPIDERMAL GROWTH-FACTOR RECEPTOR MONOCLONAL-ANTIBODIES AND CISPLATIN IN 10 HUMAN HEAD AND NECK SQUAMOUS-CELL CARCINOMA LINES

Head and neck squamous cell carcinomas (HNSCC) frequently display incr eased levels of epidermal growth factor receptor (EGFR) and since the receptor is located on the cell surface, anti-EGFR antibodies appear t o be suitable agents for antitumor therapy. We investigated the effect of murine EMD 55900 and rat ICR 62 monoclonal antibodies (MAb) direct ed against EGFR both as single agents and in combination with cisplati n. ELISA defection showed the amount of EGFR protein in HNSCC lines UM -SCC-10A, -10B, -11B, -14A, -14B, 14C, -22B and HLac 79, 8029NA, 8029D DP to range between 20 and 8100 fmol/mg protein. Compared to A431 cell s, seven HNSCC lines were high and three low receptor expressors. Only low levels of TGF alpha were found in the supernatants of some untrea ted HNSCC lines, probably due to the consumption of TGF alpha by EGFR. Consequently, occupation of EGFR by MAb led to marked accumulation of TGF alpha in cell supernatants. Colorimetric MTT assay showed both MA bs (0.3-30nM) to have comparable dose-dependent growth inhibition whic h correlated with the EGFR content of the respective cell lines (p<0.0 5). Using 30nM MAb, seven high receptor expressing HNSCC lines were gr owth inhibited by at least 20% to a maximum of 61% (mean=38%). Combine d treatment with MAb and cisplatin led to a significant decrease in ci splatin IC50 values in 5 cell lines expressing more than 1200 fmol EGF R/mg (dose modification by factor 2.1-4.1). In conclusion, anti-EGFR M Ab exert direct antiproliferative activity in HNSCC lines and show add itive effects in combination with cisplatin.