Eradication of Cultured Human Melanoma Cells by Immune Interferon and Leukocytes

Abstract

For the determination of the conditions for the most effective cytolysis of human melanoma cells, leukocyte interferon (IFN-α), fibroblast interferon (IFN-β), and immune interferon (IFN-γ) 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-γ had significantly greater direct anticellular effect than IFN-α or IFN-β. When PBL were added, all target cells were killed after 48 hours with IFN-γ, but they were not killed with IFN-α or IFN-β. When IFN-γ was added to either IFN-α or IFN-β, a potentiation of the anticellular effect was observed both with and without PBL. The actions of this “natural” IFN-γ could be reproduced with recombinant IFN-γ and could be neutralized by an antibody to a synthetic peptide encoded by the 5′-end of IFN-γ complementary DNA. It was concluded that IFN-γ is Significantly more active against these human melanoma cell lines than either IFN-α or IFN-β and, most significantly, that eradication can occur in the presence of IFN-γ and PBL. Furthermore, synergistic anticellular action can be observed when IFN-γ is added to IFN-α or IFN-β. These findings pOint to the need for preclinical trials to evaluate eradication in vivo.