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Development of a therapeutic vaccine targeting Merkel cell polyomavirus capsid protein VP1 against Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a high mortality rate, while Merkel cell polyomavirus (MCV) has been pointed as the causative agent of MCC. A better prognosis of MCC associated with a high level of antibodies against the capsid protein VP1 suggests that anti-VP1...

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Autores principales: Xu, Dan, Jiang, Sheng, He, Yue, Jin, Xiang, Zhao, Gan, Wang, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492671/
https://www.ncbi.nlm.nih.gov/pubmed/34611173
http://dx.doi.org/10.1038/s41541-021-00382-9
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author Xu, Dan
Jiang, Sheng
He, Yue
Jin, Xiang
Zhao, Gan
Wang, Bin
author_facet Xu, Dan
Jiang, Sheng
He, Yue
Jin, Xiang
Zhao, Gan
Wang, Bin
author_sort Xu, Dan
collection PubMed
description Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a high mortality rate, while Merkel cell polyomavirus (MCV) has been pointed as the causative agent of MCC. A better prognosis of MCC associated with a high level of antibodies against the capsid protein VP1 suggests that anti-VP1 immune response might be essential against MCC growth. In the current study, we developed a VP1-target vaccine formulated with CRA. Using a tumorigenic CMS5-VP1 tumor model, the vaccine-induced a potent antitumor efficacy in a dose-dependent manner was evidently demonstrated and mainly mediated by both VP1-specific CD4(+ )and CD8(+ )T-cell responses against the growth of CMS5-VP1 tumors in vaccinated BALB/c mice since the depletion of CD4(+ )and CD8(+ )T cells reverse the antitumor effects. Thus, immunotherapy with this vaccine represents a novel approach for the clinical treatment of aggressive MCV-related MCC in humans.
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spelling pubmed-84926712021-10-07 Development of a therapeutic vaccine targeting Merkel cell polyomavirus capsid protein VP1 against Merkel cell carcinoma Xu, Dan Jiang, Sheng He, Yue Jin, Xiang Zhao, Gan Wang, Bin NPJ Vaccines Article Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a high mortality rate, while Merkel cell polyomavirus (MCV) has been pointed as the causative agent of MCC. A better prognosis of MCC associated with a high level of antibodies against the capsid protein VP1 suggests that anti-VP1 immune response might be essential against MCC growth. In the current study, we developed a VP1-target vaccine formulated with CRA. Using a tumorigenic CMS5-VP1 tumor model, the vaccine-induced a potent antitumor efficacy in a dose-dependent manner was evidently demonstrated and mainly mediated by both VP1-specific CD4(+ )and CD8(+ )T-cell responses against the growth of CMS5-VP1 tumors in vaccinated BALB/c mice since the depletion of CD4(+ )and CD8(+ )T cells reverse the antitumor effects. Thus, immunotherapy with this vaccine represents a novel approach for the clinical treatment of aggressive MCV-related MCC in humans. Nature Publishing Group UK 2021-10-05 /pmc/articles/PMC8492671/ /pubmed/34611173 http://dx.doi.org/10.1038/s41541-021-00382-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Xu, Dan
Jiang, Sheng
He, Yue
Jin, Xiang
Zhao, Gan
Wang, Bin
Development of a therapeutic vaccine targeting Merkel cell polyomavirus capsid protein VP1 against Merkel cell carcinoma
title Development of a therapeutic vaccine targeting Merkel cell polyomavirus capsid protein VP1 against Merkel cell carcinoma
title_full Development of a therapeutic vaccine targeting Merkel cell polyomavirus capsid protein VP1 against Merkel cell carcinoma
title_fullStr Development of a therapeutic vaccine targeting Merkel cell polyomavirus capsid protein VP1 against Merkel cell carcinoma
title_full_unstemmed Development of a therapeutic vaccine targeting Merkel cell polyomavirus capsid protein VP1 against Merkel cell carcinoma
title_short Development of a therapeutic vaccine targeting Merkel cell polyomavirus capsid protein VP1 against Merkel cell carcinoma
title_sort development of a therapeutic vaccine targeting merkel cell polyomavirus capsid protein vp1 against merkel cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492671/
https://www.ncbi.nlm.nih.gov/pubmed/34611173
http://dx.doi.org/10.1038/s41541-021-00382-9
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