INTERFERON-GAMMA IS HIGHLY EFFECTIVE AGAINST ORTHOTOPICALLY-IMPLANTEDHUMAN PLEURAL ADENOCARCINOMA IN NUDE-MICE

The efficacy of recombinant human gamma interferon (rh IFN-gamma) was evaluated for the treatment of human pleural adenocarcinoma in a patie nt-like nude mice model which is constructed by surgical orthotopic im plantation (SOI) of histologically-intact human tumor tissue. The huma n non-small-cell lung cancer cell line H-460 was used for the study Ga mma interferon was tested in three different dosages (25,000 U, 50,000 U and 100,000 U) versus an untreated control through i.p. injection t wice a day for five days, which was started 48 hours after SOI; The re sults showed that IFN-gamma can prolong the survival time of the tumor -bearing animals. The symptoms and signs of hypoxia such as restricted physical activity and cyanosis due to primary tumor growth in the tho racic cavity as well as cachexia developed much earlier in the control than in the IFN-gamma-treated mice. The mice in the control group had succumbed by day-23 after tumor implantation, however at that time 67 % of the mice in the 100,000 U-treated group, 15% of the mice in the 5 0,000 U-treated group, and 16% of the mice in the 25,000 U-treated gro up were still alive. The orthotopically-transplanted tumor grew rapidl y and metastasized to the lung and liver in the untreated control. In the IFN-gamma-treated groups both primary tumor growth and metastasis were reduced, probably accounting for the increased survival rate. The results demonstrated dose-dependent efficacy of IFN-gamma in suppress ing symptomology, primary tumor growth, invasiveness and metastasis of the human lung cancer cell line H 460, and ina eased survival of the tumor-bearing animals. These results suggest clinical trials of IFN-ga mma should begin for treatment of pleural adenocarcinoma for which the re is no current effective therapy.