IFN-alpha and novel strategies of combination therapy for cancer

Interferons-alpha (IFN-alpha) are a group of cytokines belonging to type I IFN family, which exert multiple biological effects, including antiviral and antitumor activities in patients with defined types of cancer and viral diseases. Early studies in mouse tumor models have shown the importance of host immune mechanisms in the generation of a long-lasting antitumor response after type I IFN treatment. Recent studies have revealed new immunomodulatory effects of IFN-alpha, including activities on T cells and dendritic cells (DCs), which may explain the immune correlates frequently observed in some categories of cancer patients responding to IFN-alpha therapy. Of note, new knowledge has recently been generated on the mechanisms of action of some chemotherapeutic agents, such as cyclophosphamide (CTX), on cells of the immune system, whose effects can now be exploited for the design of more effective combination therapies. On the whole, the new strategies based on IFN-alpha include the in vivo use of these cytokines as immune adjuvants of cancer vaccines, their in vitro use to generate highly active DC-based vaccines, and the combination of certain chemotherapy regimens with IFN-alpha-adjuvanted cancer vaccines.