Growth inhibition of breast cancer cell lines by combinations of anti-P185^HER2 monoclonal antibody and cytokines

The p185^HER2 oncogene is associated with poor prognosis in patients with breast cancer. Both anti-p185^HER2. MAb and cytokines have been shown to downregulate p185^HER2 expression. We investigated the effect of combinations of humanized 4D5, an anti-p185^HER2 MAb, and the cytokines IFN-α, IFN-γ or TNF-α on the growth of three p185^HER2 positive human breast carcinoma cell lines, SK-BR-3, BT-474, and MDA-MB-453. All three cell lines were treated with IFN-α (1000 U/ml) or IFN-γ (1000 U/ml) or TNF-α (100 U/ml) with or without huMAb 4D5 (100 μM), and cell growth was determined on days 3-7. While IFN-α, IFN-γ. TNF-α, and huMAb 4D5 all inhibited growth, an apparently additive inhibitory effect occurred using combinations of huMAb 4D5 plus cytokine, with huMAb 4D5 plus TNF-α causing the greatest growth inhibition. These results demonstrate the potentiation of growth inhibition of breast cancer cell lines by the combination of anti p185^HER2 MAb and cytokines, and suggest that combinations of anti-growth factor receptor MAb and cytokines may be useful in the treatment of breast cancer.