[Induction of tumoricidal properties in human monocytes by synergism between interferon-gamma and liposome-entrapped muramyl tripeptide]

Abstract

Human blood monocytes from healthy volunteers, separated by centrifugal elutriation, were not cytotoxic to allogeneic A 375 melanoma cells. The monocytes were rendered tumoricidal by incubation for 24 h with natural interferon-alpha and beta or recombinant interferon-alpha A and alpha A/D (more than 100 U/ml) or with interferon-gamma (more than 1 U/ml). Liposome-MTP-PE at concentrations of more than 50 nmol/ml also induced tumoricidal activity of monocytes. When a combination of subthreshold concentrations of these IFNs and liposome-MTP-PE were added to monocyte cultures, IFN-alpha and beta acted additively in monocyte activation, while IFN-gamma acted synergistically. The synergism for monocyte activation required that monocytes be incubated first with IFN-gamma and then with liposome-MTP-PE. These findings suggest that the synergistic effect of IFN-gamma and liposome-MTP-PE can decrease the necessary clinical doses of these agents for malignant diseases, and may have therapeutic availability in the treatment of metastatic cancer in humans.