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Chimeric HBcAg virus-like particles presenting a HPV 16 E7 epitope significantly suppressed tumor progression through preventive or therapeutic immunization in a TC-1-grafted mouse model

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      Abstract

      Background

      Therapeutic human papillomavirus (HPV) vaccines are currently being developed. However, no therapeutic efficacy has been achieved in clinical trials for the treatment of cervical intraepithelial neoplasia or cancer. One of the important issues in increasing vaccine efficacy is determining the best way to enhance tumor antigen-specific cellular immune responses. This study aimed to explore the virus-like particles (VLPs) of hepatitis B core antigen (HBcAg) as potential therapeutic vaccine carriers and to assess its immunological characteristics.

      Methods

      Chimeric VLPs presenting a HPV 16 cytotoxic T lymphocytes epitope E7 49–57 (amino acid 49–57 of the E7 protein) were prepared using recombinant genes. C57BL/6 mice were immunized with VLPs and grafted with tumor cells TC-1 which is an E7-expressing tumorigenic cell line. The dynamic tumor growth was monitored and anti-tumor immune responses were investigated.

      Results

      Using a preventive strategy, immunization with VLPs resulted in nearly complete suppression of tumor growth. In treatment studies, VLP immunization significantly suppressed the tumor progression in mice carrying 2–3 mm tumors and in those bearing even larger tumors with diameters up to 8–9 mm. The VLP structure was shown to be important to induce vigorous antitumor immunity and effects. In immunized mice, enhanced E7 49–57-specific cellular immune responses were evidenced by increased interferon (IFN)-γ expression and decreased interleukin (IL)-4 expression in splenic lymphocytes, as well as an elevated number of effector cells expressing IFN-γ in response to the in vitro stimulation of the specific peptide E7 49–57. In addition, effective immune memory after VLP immunization was maintained for at least 16 weeks, preventing significant tumor growth after subsequent TC-1 challenge.

      Conclusion

      While VLPs were highly immunogenic in stimulating humoral immunity, our results strongly indicated that VLPs, such as HBcAg particles, might also be potent therapeutic vaccine carriers to elicit robust cellular immune responses, even in the immunosuppressive microenvironment of a tumor.

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      Most cited references 30

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            Author and article information

            Affiliations
            [1 ]Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, People’s Republic of China
            [2 ]Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Kunming, People’s Republic of China
            [3 ]Yunnan Engineering Research Center of Vaccine Research and Development on Severe Infectious Disease, Kunming, People’s Republic of China
            Author notes
            Correspondence: Yanbing Ma, Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, 935 Jiaoling Road, Kunming 650118, People’s Republic of China, Tel +86 871 6833 9287, Fax +86 871 6833 4483, Email mayanbing1969@ 123456hotmail.com
            [*]

            These authors contributed equally to this work

            Journal
            Int J Nanomedicine
            Int J Nanomedicine
            International Journal of Nanomedicine
            International Journal of Nanomedicine
            Dove Medical Press
            1176-9114
            1178-2013
            2016
            27 May 2016
            : 11
            : 2417-2429
            27313455
            4892837
            10.2147/IJN.S102467
            ijn-11-2417
            © 2016 Chu et al. This work is published and licensed by Dove Medical Press Limited

            The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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            Original Research

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