Synergism of recombinant human interferon gamma with liposome-encapsulated muramyl tripeptide in activation of the tumoricidal properties of human monocytes.

Freshly isolated human peripheral blood monocytes from healthy volunteers are not cytotoxic to allogeneic A375 melanoma cells, but they were rendered tumoricidal by incubation in vitro with either liposomes containing 5 micrograms/mumol phospholipid of muramyl tripeptide phosphatidylethanolamine (liposome-MTP-PE; optimal dose, 500 nmol/ml) or recombinant human interferon gamma (rIFN-gamma; optimal dose, 100 U/ml). A combination of sub-threshold concentrations of liposome-MTP-PE (50 nmol/ml) and rIFN-gamma (1 or 10 U/ml) also induced significant tumor-cell killing, indicating that the effects of rIFN-gamma and liposome-MTP-PE in monocyte activation are synergistic. In contrast to rIFN-gamma, recombinant IFN-alpha and IFN-beta had additive effects with liposome-MTP-PE in human monocyte activation. Since recombinant human IFN-gamma has a synergistic effect with liposome-MTP-PE in monocyte activation, unlike IFN-alpha or IFN-beta, and liposome-MTP-PE as well as rIFN-gamma is available at standardized concentrations, this combination could be of clinical value in the treatment of disseminated malignant disease.