Antitumor potential of interferon-gamma: retroviral expression of mouse interferon-gamma cDNA in two kinds of highly metastatic mouse tumor lines reduces their tumorigenicity.

The antitumor effects of interferon (IFN)-gamma were examined in two types of malignant metastatic mouse tumor cell lines following their transfection with the IFN-gamma gene by retroviral gene transfer. In both ovarian and lung tumor lines, but more markedly in the latter, subcutaneous (s.c.) tumor progression of the IFN-gamma-producing cells was profoundly suppressed in the normal syngeneic as well as in athymic nude mice. In addition, experimental metastasis via the tail vein of the IFN-gamma producers was also suppressed. Lung tumor suppression was abolished by X-irradiation of the syngeneic mice or by the administration of antiasialoganglioside GM1 antibodies into the nude mice. These results suggest that tumor suppression is due to the effect of the tumor-derived IFN-gamma on the host antitumor mechanisms including natural killer cells. Moreover, tumorigenicity of several unrelated tumor cells was significantly reduced when s.c. injected as a mixture with the apparently benign IFN-gamma-producing lung tumor cells, so that such 'non-malignant' IFN-gamma-producing cells may have therapeutic benefit against certain other malignant tumors.