Potent Therapeutic Efficacy of a Novel HPV16E7-HBcAg-Hsp65 Fusion Protein Vaccine

Vaccine Research

关键词: human papillomaviruses;    therapeutic vaccine;    cervical caner;    t-cell response;    combination therapy;   

DOI  :  10.52547/vacres.8.1.60

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown