MODULATION OF ASSOCIATED OVARIAN-CARCINOMA ANTIGENS BY 5 CYTOKINES USED AS SINGLE AGENTS OR IN COMBINATION

Optimization of intraperitoneal radioimmunotherapy of ovarian cancer d epends on increasing the antigenic expression of tumor cells. For this purpose, we studied the effect of 5 cytokines (IFN-alpha, IFN-beta, I FN-gamma, TNF-alpha and TGF-beta), used as single agents or in combina tion, on 4 ovarian cancer cell lines which present different antigenic profiles with the monoclonal antibodies (MAbs) tested (OC125, OVTL-3, MOv 18 and MOv 19). Analyses were performed by flow cytometry and the Scatchard technique in order to study antigenic modulation. The effec t on proliferation was determined by cell counting. Expression of O3 a ntigen, recognized by the OVTL3 MAb, was increased up to 2.5 times aft er IFNs and TNF-alpha (used as single agent) on the 2 lines presenting low basal expression (SHIN-3 and IGROVI). The expression of CA125 ant igen and the antigens recognized by MOv 18 and MOv 19 MAbs was not inc reased by any of the cytokines tested. The combination IFN-gamma + TNF -alpha was synergistic on cytotoxicity and enhanced O3 expression, pro viding 10 times as many sites per cell on the SHIN-3 line. For 3 other associations (IFN-alpha + IFN-gamma, IFN-beta + IFN-gamma and IFN-alp ha + TNF-alpha), there was an additive effect on 03 expression and on cell cytotoxicity. (C) 1994 Wiley-Liss, Inc.