A Monoclonal Antibody against the c-erbB-2 Protein Enhances the Cytotoxicity of c/5-Diamminedichloroplatinum against Human Breast and Ovarian Tumor Cell Lines

A monoclonal antibody ("IAli 250) specific to an extracellular epitope of the c-erbB-2 protein (gplSS) inhibited the in vitro proliferation of human breast tumor cell lines that overexpress c-erbB-2 in a dosedependent manner. Treatment of cells with combinations of CM-diammedichloroplatinum (CDDP) and l'Ali 250 resulted in a significantly en hanced cytotoxic effect. This synergistic cytotoxicity was apparent over a wide range of antibody concentrations (200 pg/ml-100 «¿g/ml) including concentrations that showed no inhibitory effect alone. TAb 250 did not increase the cytotoxic effect of CDDP in a cell line exhibiting no detect able level of gpl85. Athymic mice bearing s.c. xenografts of human tumor cells expressing high levels of gpl85 showed a greatly enhanced inhibition of tumor growth when treated with TAb 250 and CDDP compared to treatment with the antibody or CDDP alone. This effect was specific inasmuch as TAb 250 did not enhance the growth-inhibitory effect of CDDP on tumor xenografts which were not expressing gplSS.