Interferon gamma is highly effective against orthotopically-implanted human 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 patient-like nude mice model which is constructed by surgical orthotopic implantation (SOI) of histologically-intact human tumor tissue. The human non-small-cell lung cancer cell line H-460 was used for the study. Gamma 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 twice a day for five days, which was started 48 hours after SOI; The results 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 thoracic 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 50,000 U-treated group, and 16% of the mice in the 25,000 U-treated group were still alive. The orthotopically-transplanted tumor grew rapidly 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 suppressing symptomology, primary tumor growth, invasiveness and metastasis of the human lung cancer cell line H 460, and increased survival of the tumor-bearing animals. These results suggest clinical trials of IFN-gamma should begin for treatment of pleural adenocarcinoma for which there is no current effective therapy.