Human recombinant alpha- and gamma-interferons enhance the cytotoxic properties of tumor necrosis factor on human melanoma.

Three short-term human melanoma cell lines were tested for sensitivity to human recombinant alpha-tumor necrosis factor (TNF) in a semisolid agar colony formation assay. Cells from three pigmented and one amelanotic strain displayed low sensitivity to TNF. The ID50 for the inhibition of melanoma colony formation ranged from 2,500 to 20,000 U/ml. We then tested the ability of human recombinant alpha-interferon (IFN-alpha) and gamma-interferon (IFN-gamma) to interact with TNF to inhibit melanoma colony formation. Analysis of the TNF-IFN mixtures using the median effect method demonstrated that both IFNs interacted synergistically with TNF to inhibit melanoma colony formation. On a unit basis, IFN-gamma was more active with TNF than IFN-alpha. The addition of the second interferon to the mixture enhanced the ability of TNF to promote the cytolysis of human melanoma cells. The enhanced killing effect seen with the combination of IFN-alpha, IFN-gamma, and TNF suggests an interesting strategy for the treatment of human melanoma.