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 huma n recombinant interferon-gamma (hrlFN-gamma) can act synergically with various activators in increasing the cytotoxicity of cancer patient m onocytes against fresh autologous and allogeneic tumor cells. Methods: Fresh target cells were obtained by means on the mechanical and enzym atic dissociation of human renal carcinomas. A 375 and SW 626 cell lin es were used as positive controls. Monocytes from renal cancer patient s and normal volunteers were activated in vitro with lipopolysaccharid e, 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. Result s: Cancer patient peripheral blood monocytes were activated in vitro b y different immunomodulators and became cytotoxic to freshly dissociat ed autologous or allogeneic tumor cells. A synergic effect producing m aximal cytotoxicity was obtained with an appropriately scheduled combi nation 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 tumo r 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 immunom odulators and that the low levels of hrIFN-gamma required for the syne rgic activation are not toxic in vivo.