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Introduction: Cervical cancer is the fourth leading cause of cancer death in women worldwide. Nearly all cervical cancers are resulted from high-risk Human Papillomavirus (HPV) infection. Currently, there is no available HPV-specific therapy. Cancer therapeutic vaccines have shown anti-tumor efficacy in preclinical animal models as well as clinical patients. Methods: Here, we used a previously-reported therapeutic vaccine candidate (VR₁₁₁) based on HPV16E7-HBcAg-Hsp65 fusion protein (with aluminum hydroxide adjuvant) and injected mice with 2 doses of VR₁₁₁ at a two-week interval 2 days after TC-1 tumor cell implantation. Tumor growth and animal survival rates were monitored and the vaccine-associated immune responses were evaluated by cytotoxic T lymphocytes assay, T-cell proliferation assay and CD4⁺/CD8⁺ T-cell depletion. Results: In TC-1 tumor murine model, VR₁₁₁ vaccine showed potent dose dependent therapeutic efficacy against tumor growth and improved survival rates in the medium (10 μg) and high doses (30 μg). The three fusion components of VR₁₁₁ were all necessary to induce the best anti-tumor activity, CTL response and T cell proliferation. The tumor growth inhibition and a higher mouse survival rate were among the beneficial effects of cisplatin-based combination treatment. Moreover, the anti-tumor potency of VR₁₁₁ vaccine was proved to be significantly associated with E7 specific CD8⁺ T cell immune response and the adoptive lymphocyte transfer therapy also showed tumor growth inhibition. Conclusion: The results confirmed VR₁₁₁ as a potent therapeutic HPV vaccine candidate with superior anti-tumor efficacy in a murine model of HPV-induced cancer which its potentials could be considered for combination therapies against cervical cancer.

Keywords: Human papillomaviruses, Therapeutic vaccine, Cervical caner, T-cell response, Combination therapy

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