[85] Animal models for investigating antitumor effects of interferon

Publisher Summary This chapter discusses animal models for investigating antitumor effects of interferon. Animal tumor models have been important in the development of many cancer therapies and catalytic in the current upsurge of clinical interest in interferons (IFNs). Murine IFNs of varying degrees of purity increased survival time or reduced tumor size of mice implanted with many murine tumor cell lines, showing an activity broadly comparable to single agent chemotherapy. Investigations into the mechanisms of this antitumor activity are complex, because IFNs are regulatory agents capable of directly influencing cellular proliferation and differentiation, directly protecting cells from viral infection and transformation and indirectly inhibiting tumor growth by enhancing host reaction to the tumor. In animal model systems, all three mechanisms may be important. The dissociation of IFN effects on the tumor from effects on the host that can be achieved by using mouse and human IFNs has also proved useful in investigating the mechanism of the synergy seen between IFN and chemotherapy. Chemotherapeutic drugs are metabolized, by the host, particularly in the liver, and the balance between activation and detoxification is important in determining activity.