In Vitro Synergic Effect of Interferon Gamma Combined with Liposomes Containing Muramyl Tripeptide on Human Monocyte Cytotoxicity Against Fresh Allogeneic and Autologous Tumor Cells.

Aims: The purpose of the present study was to investigate whether human recombinant interferon-gamma (hrlFN-gamma) can act synergically with various activators in increasing the cytotoxicity of cancer patient monocytes against fresh autologous and allogeneic tumor cells. Methods: Fresh target cells were obtained by means on the mechanical and enzymatic dissociation of human renal carcinomas. A 375 and SW 626 cell lines were used as positive controls. Monocytes from renal cancer patients and normal volunteers were activated in vitro with lipopolysaccharide, muramyl tripeptide (MTP-PE) or liposomes containing MTP-PE (MTP-PE liposomes), with or without a pre-incubation with hrlFN-gamma and were tested for cytotoxicity by means of a 72-hr (111)indium-release assay. All of the patients were tumor free at the time of the study. Results: Cancer patient peripheral blood monocytes were activated in vitro by different immunomodulators and became cytotoxic to freshly dissociated autologous or allogeneic tumor cells. A synergic effect producing maximal cytotoxicity was obtained with an appropriately scheduled combination of hrlFN-gamma (10 U/ml) and MTP-PE liposomes (50 nm/ml), free lipopolysaccharide (10 mu g/ml) or MTP-PE (100 mu g/ml). The synergic cytotoxicity was observed against fresh allogeneic and autologous tumor cells, as well as against cultured cells. Conclusions: All of these data support the possibility of a combined treatment using hrlFN-gamma and MTP-PE liposomes in human studies, particularly when if is borne in mind that liposomes can prevent the direct toxicity of many immunomodulators and that the low levels of hrIFN-gamma required for the synergic activation are not toxic in vivo.