Cancer immunotherapy: the interferon-alpha experience

Abstract

Interferons are agents with antiviral, antiproliferative, and immunomodulatory properties. Interferon-alfa (IFN-alpha) is used in the treatment of hematologic malignancies and solid tumors. IFN-alpha has shown antitumor and antiviral efficacy that are not correlated, one with another. Approval by the US Food and Drug Administration was granted early for the treatment of patients with hairy cell leukemia, acquired immune deficiency syndrome-related Kaposi's sarcoma, and condylomata acuminata. Although IFNs are effective as single agents in certain clinical pathologic entities, increasing experience with these cytokines suggests that their greatest therapeutic potential may be realized in combination with other biological response modifiers, cytotoxics, or antiviral agents. For example, trials combining IFN-alpha with 5-fluorouracil to treat colorectal carcinoma or IFN-alpha with zidovudine to treat acquired immune deficiency disorder showed increased efficacy over IFN-alpha alone. While IFN-alpha appears to be moderately effective in certain diseases, the flu-like syndrome associated with its use is a major limiting factor for its clinical application. Further studies are needed to determine the underlying mechanism of action for IFNs and the most effective combinations and appropriate preclinical models, or intermediate endpoints that will then facilitate the rational use of this agent in combinations based on the mechanisms of action of IFN-alpha.