Differential action of six human interferons against two human carcinomas growing in nude mice

Six different pure human interferons (IFNs), were tested for anti-tumour effect against two human carcinomas, breast and bowel, growing in nude mice, in a total of 36 experiments. The IFN-alpha mixture, analogue and subtypes showed the greatest activity, particularly against the breast cancer xenograft, whereas IFN-beta and IFN-gamma had little effect. However, circulating IFN could be found in the sera of mice treated with all 3 IFN types. In terms of amount of IFN protein, IFN-alpha Con1, an IFN-alpha analogue, was the most effective, a dose of 0.1 micrograms/mouse/day being sufficient to induce breast tumour regression, and IFN-gamma the least effective, a dose of 10 micrograms/mouse/day having no effect on the same tumour. A more detailed comparison of 2 IFN-alpha subtypes showed that a daily dose of 1 microgram IFN-alpha A was more effective than the same dose of IFN-alpha D, but as this IFN had approximately 30 times less antiviral activity on human cells than IFN-alpha D, these IFNs were probably at least equally effective in terms of human cell units. IFN-alpha D stimulated mouse spleen natural killer cell activity but it was not clear whether this stimulation was involved in anti-tumour activity. We conclude that this model system is useful for investigating direct anti-tumour activity of a wide range of IFN types and subtypes.