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Treatment with Imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination

There is an urgent need to develop new innovative therapies for the control of advanced cancer. The combination of antigen-specific immunotherapy with the employment of immunomodulatory agents has emerged as a potentially plausible approach for the control of advanced cancer. Methods: In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) with the TLR7 agonist imiquimod for their ability to generate E7-specific immune responses and antitumor effects in tumor-bearing mice. Results: We observed that treatment with CRT/E7 DNA in combination with imiquimod leads to. | Chuang et al. Journal of Biomedical Science 2010 17 32 http www.jbiomedsci.eom content 17 1 32 a NSC The cost of publication In Journal of Blomodlcal Science Is boms by tlM National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Treatment with Imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination Chi-Mu Chuang 1 5 6 Archana Monie1 Chien-Fu Hung1 2 and T-C Wu 1 2 3 4 Abstract Background There is an urgent need to develop new innovative therapies for the control of advanced cancer. The combination of antigen-specific immunotherapy with the employment of immunomodulatory agents has emerged as a potentially plausible approach for the control of advanced cancer. Methods In the current study we explored the combination of the DNA vaccine encoding calreticulin CRT linked to human papillomavirus type 16 HPV-16 E7 antigen CRT E7 with the TLR7 agonist imiquimod for their ability to generate E7-specific immune responses and antitumor effects in tumor-bearing mice. Results We observed that treatment with CRT E7 DNA in combination with imiquimod leads to an enhancement in the E7-specific CD8 T cell immune responses and a decrease in the number of myeloid-derived suppressor cells in the tumor microenvironment of tumor-bearing mice. Furthermore treatment with CRT E7 DNA in combination with imiquimod leads to significantly improved antitumor effects and prolonged survival in treated mice. In addition treatment with imiquimod led to increased number of NK1.1 cells and F4 80 cells in the tumor microenvironment. Macrophages and NK1.1 cells were found to play an important role in the antitumor effects mediated by treatment with CRT E7 DNA in combination with imiquimod. Conclusions Thus our data suggests that the combination of therapeutic HPV DNA vaccination with topical treatment with the TLR7 agonist imiquimod enhances the antitumor immunity induced by DNA vaccination. The current study has significant implications for future .