Administration of IFN-A Enhances the Efficacy of a Granulocyte Macrophage Colony Stimulating Factor–Secreting Tumor Cell Vaccine

IFN-A 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-A delivered at the vaccine site. Similarly, 80% of mice treated with the combination reject established B16 tumors when recombinant murine IFN-A 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 Tcells was observed inmice treated with the combinationwhen compared with unvaccinated controls. These data show that IFN-A combined with a granulocyte macrophage colonystimulating factor–secreting tumor cell vaccine significantly enhances vaccine potency and may represent a potential new approach for tumor immunotherapy. (Cancer Res 2005; 65(6): 2449-56)