Administration of IFN-alpha enhances the efficacy of a granulocyte macrophage colony stimulating factor-secreting tumor cell vaccine

IFN-alpha is approved for the treatment of multiple cancers. Its pleiotropic properties include inhibition of proliferation and angiogenesis and induction of apoptosis. Type I IFNs also exert immunomodulatory effects, which make it an appropriate candidate to combine with cancer vaccines. The studies reported herein show that 50% of mice reject established B16 tumors following treatment with the combination of a granulocyte macrophage colony-stimulating factor-secreting tumor cell vaccine (B16.GM) and subclinical doses of recombinant murine IFN-alpha delivered at the vaccine site. Similarly, 80% of mice treated with the combination reject established B16 tumors when recombinant murine IFN-alpha is given at the challenge site, suggesting that in the latter case its antiproliferative, proapoptotic, and antiangiogenic properties may be involved in controlling tumor growth. In contrast, fewer than 10% of mice reject the tumors when either one is used as a monotherapy. Furthermore, a 30-fold increase in the frequency of melanoma-associated antigen (Trp-2 and gp100) specific T cells was observed in mice treated with the combination when compared with unvaccinated controls. These data show that IFN-alpha combined with a granulocyte macrophage colony-stimulating factor-secreting tumor cell vaccine significantly enhances vaccine potency and may represent a potential new approach for tumor immunotherapy.