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
Xiaojie Chu,1–3,* Yang Li,1–3,* Qiong Long,1–3 Ye Xia,1–3 Yufeng Yao,1–3 Wenjia Sun,1–3 Weiwei Huang,1–3 Xu Yang,1–3 Cunbao Liu,1–3 Yanbing Ma1–3 1Laboratory of Molecular Immunology, Institute of Med...
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Dove Medical Press
2016
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oai:doaj.org-article:df6602a4733849ea910d2c3ddba140212021-12-02T05:14:21ZChimeric 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 model1178-2013https://doaj.org/article/df6602a4733849ea910d2c3ddba140212016-05-01T00:00:00Zhttps://www.dovepress.com/chimeric-hbcag-virus-like-particles-presenting-a-hpv-16-e7-epitope-sig-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaojie Chu,1–3,* Yang Li,1–3,* Qiong Long,1–3 Ye Xia,1–3 Yufeng Yao,1–3 Wenjia Sun,1–3 Weiwei Huang,1–3 Xu Yang,1–3 Cunbao Liu,1–3 Yanbing Ma1–3 1Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, 2Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, 3Yunnan Engineering Research Center of Vaccine Research and Development on Severe Infectious Disease, Kunming, People’s Republic of China *These authors contributed equally to this work 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 E749–57 (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 E749–57-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 E749–57. 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. Keywords: cellular immune responses, human papillomavirus, tumor, therapeutic vaccine, virus-like particlesChu XLi YLong QXia YYao YSun WHuang WYang XLiu CMa YDove Medical Pressarticlecellular immune responseshuman papillomavirus (HPV)tumortherapeutic vaccinevirus-like particles (VLPs)Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 2417-2429 (2016) |
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cellular immune responses human papillomavirus (HPV) tumor therapeutic vaccine virus-like particles (VLPs) Medicine (General) R5-920 |
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cellular immune responses human papillomavirus (HPV) tumor therapeutic vaccine virus-like particles (VLPs) Medicine (General) R5-920 Chu X Li Y Long Q Xia Y Yao Y Sun W Huang W Yang X Liu C Ma Y 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 |
| description |
Xiaojie Chu,1–3,* Yang Li,1–3,* Qiong Long,1–3 Ye Xia,1–3 Yufeng Yao,1–3 Wenjia Sun,1–3 Weiwei Huang,1–3 Xu Yang,1–3 Cunbao Liu,1–3 Yanbing Ma1–3 1Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, 2Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, 3Yunnan Engineering Research Center of Vaccine Research and Development on Severe Infectious Disease, Kunming, People’s Republic of China *These authors contributed equally to this work 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 E749–57 (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 E749–57-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 E749–57. 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. Keywords: cellular immune responses, human papillomavirus, tumor, therapeutic vaccine, virus-like particles |
| format |
article |
| author |
Chu X Li Y Long Q Xia Y Yao Y Sun W Huang W Yang X Liu C Ma Y |
| author_facet |
Chu X Li Y Long Q Xia Y Yao Y Sun W Huang W Yang X Liu C Ma Y |
| author_sort |
Chu X |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
Dove Medical Press |
| publishDate |
2016 |
| url |
https://doaj.org/article/df6602a4733849ea910d2c3ddba14021 |
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