Effect of human recombinant tumour necrosis factor and rat gamma interferon on nitrosomethylurea-induced mammary tumours.

We have used the nitrosomethylurea-induced rat mammary tumour model to study the effects of parenteral administration of human recombinant tumour necrosis factor (rHu-TNF) and rat gamma interferon (IFN-gamma). An inbred strain of tumour bearing female Ludwig/Wistar/Olac rats were randomised to either treatment or control groups. Two independent studies showed that combined treatment with rHu-TNF and rat IFN-gamma induced significant tumour regression over 4 weeks (P = 0.004, P = 0.005 respectively). Treatment with either rHu-TNF or rat IFN-gamma given individually did not affect the overall rate of tumour growth (P = 0.157 and 0.40 respectively) although an initial reduction in tumour size was observed during the first few days after injection. Measurement of circulating oestradiol levels in groups in which maximum tumour regression was observed showed no statistically significant difference when compared to the control group. Similarly, measurement of oestrogen receptor content showed no statistically significant difference between rHu-TNF-gamma or rat-IFN-gamma treatment or combined treatment of rHu-TNF and IFN-gamma with the control group. We conclude from these observations that combined therapy with rHu-TNF and rat IFN-gamma may prove to be useful new forms of treatment for human breast cancer.