Antiproliferative effects of natural interferon beta alone and in combination with natural interferon gamma on human breast carcinomas in nude mice

Nude mice bearing bilateral xenografts of human breast carcinoma cells (MCF-7 and BT20) were treated with 2 or 4 5-day cycles of intralesional (i.l.) injections of human natural interferon beta (nIFN-β) alone or in combination with human natural interferon gamma (nIFN-γ). The injections were administered to only 1 of the 2 tumors in each animal, thus making it possible to assess at the same time local therapeutic effects in the injected tumors and systemic effects in the contralateral ones. When n-IFN-β was used as a single agent only mild local antitumor effects and virtually no systemic effects were observed. In contrast, the combined administration of nIFN-β/nIFN-γ produced marked antiproliferative effects, presumably as a result of the synergistic action of type I and type II IFNs. These effects ranged from complete regression documented histologically in 2 MCF-7 tumors to varying degrees of growth inhibition with persistence of residual microscopic or grossly detectable tumor. Local effects were more pronounced than systemic effects. The therapeutic efficacy of nIFN-β proved to be greater than that of recombinant interferon beta (rIFN-β). In MCF-7 tumors nIFN-β appeared to be less effective than nIFN-α, whereas the opposite was true for BT 20 tumors.