Eradication of cultured human melanoma cells by immune interferon and leukocytes

For the determination of the conditions for the most effective cytolysis of human melanoma cells, leukocyte interferon (IFN-alpha), fibroblast interferon (IFN-beta), and immune interferon (IFN-gamma) were compared for their abilities to kill cultured human melanoma cells in the presence and absence of peripheral blood mononuclear leukocytes (PBL). A microassay was employed in which the viability of melanoma target cells was determined after various times of incubation with interferons alone or with PBL. On 7 human melanoma cell lines (from 6 different patients), IFN-gamma had significantly greater direct anticellular effect than IFN-alpha or IFN-beta. When PBL were added, all target cells were killed after 48 hours with IFN-gamma, but they were not killed with IFN-alpha or IFN-beta. When IFN-gamma was added to either IFN-alpha or IFN-beta, a potentiation of the anticellular effect was observed both with and without PBL. The actions of this "natural" IFN-gamma could be reproduced with recombinant IFN-gamma and could be neutralized by an antibody to a synthetic peptide encoded by the 5'-end of IFN-gamma complementary DNA. It was concluded that IFN-gamma is significantly more active against these human melanoma cell lines than either IFN-alpha or IFN-beta and, most significantly, that eradication can occur in the presence of IFN-gamma and PBL. Furthermore, synergistic anticellular action can be observed when IFN-gamma is added to IFN-alpha or IFN-beta. These findings point to the need for preclinical trials to evaluate eradication in vivo.