Growth inhibition of breast cancer cell lines by combinations of anti-P185HER2 monoclonal antibody and cytokines.

The p185HER2 oncogene is associated with poor prognosis in patients with breast cancer. Both anti-p185HER2 MAb and cytokines have been shown to downregulate p185HER2 expression. We investigated the effect of combinations of humanized 4D5, and anti-p185HER2 MAB, and the cytokines IFN-alpha, IFN-gamma or TNF-alpha on the growth of three p185HER2 positive human abreast carcinoma cell lines, SK-BR-3, BT-474, and MDA-MB-453. All three cell lines were treated with IFN-alpha (1000 U/ml) or IFN-gamma (1000 U/ml) or TNF-alpha (100 U/ml) with or without huMAb 4D5 (100 microM), and cell growth was determined on days 3-7. While IFN-alpha, IFN-gamma, TNF-alpha, and huMAb 4D5 all inhibited growth, an apparently additive inhibitory effect occurred using combinations of huMAb 4D5 plus cytokine, with huMAb 4D5 plus TNF-alpha causing the greatest growth inhibition. These results demonstrate the potentiation of growth inhibition of breast cancer cell lines by the combination of anti p185HER2 MAb and cytokines, and suggest that combinations of anti-growth factor receptor MAb and cytokines may be useful in the treatment of breast cancer.