Interferon alpha in combination with other biologics: the scientific rationale

Interferon alpha (IFN alpha) has widely pleiotropic effects, on both the immune system and tumour cells, and any of these effects might provide the basis for additive or synergistic effects when administered in combination with other biologics. Some of the main sites of action to consider include the ability of IFN alpha to: inhibit the growth of tumour cells; induce differentiation, and/or MHC expression on tumour cells; and stimulate the activation and/or differentiation of natural killer (NK) cells, cytotoxic T lymphocytes, and cytotoxic macrophages. Other biologics with similar sites of action might be expected to provide additional effects when combined with IFN alpha, and factors with other, complementary anti-tumour effects might synergize. Potentially important therapeutic effects have been observed when IFN alpha has been combined with IFN gamma, interleukin 2, tumour necrosis factor, interleukin 1, monoclonal antibodies, and retinoids. The development of therapeutic strategies on the basis of hypotheses as to how IFN alpha might effectively interact with another biologic, coupled with careful assessment of effects on the tumour cells and/or serial monitoring of immunologic parameters, might be expected to lead most expeditiously to successful therapeutic combinations of IFN alpha with other biologics.