The main aim of this study is to evaluate the potential application of an immunomodulatory protein, Fve, as an adjuvant for tumor immunotherapy. Using HPV-16 E7 oncoprotein as a model antigen, we have demonstrated that mice co-immunized with E7 and Fve showed enhanced E7-specific antibodies as compared to mice immunized with E7 alone. Furthermore, intracellular cytokine staining revealed that there was an increased expansion of E7-specific IFN-γ-producing CD4+ and CD8+ T cells in the co-immunized mice. Tumor protection assays showed that 60% of mice co-immunized with E7 plus Fve remained tumor free up to 167 days after the TC-1 tumor cells challenge whereas only 20% of the E7-immunized mice remained tumor free. Tumor therapeutic assays showed that E7 plus Fve treatment significantly retarded tumor growth and prolonged survival of tumor bearing mice as compared to those treated by E7 alone. In the metastatic settings, similar enhanced prophylactic and therapeutic anti-tumor effects were observed in the co-immunized mice. Antibody depletion assays illustrated that the CD4+, CD8+ T cells and IFN-γ play critical roles in conferring the anti-tumor effects. Adoptive transfer of purified T cells to the tumor-bearing mice further indicated that T cells play a pivotal role in the therapeutic anti-tumor effects and such effects are correlated to the magnitude of the E7-specific T cell responses. In summary, this study demonstrates that Fve protein has potent adjuvant properties, in driving enhanced antigen-specific humoral and cellular type 1 immune responses, which confer effective anti-tumor effects, representing an attractive vaccination strategy for cancer immunotherapy.

First AACR Centennial Conference on Translational Cancer Medicine-- Nov 4-8, 2007; Singapore