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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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Detalles Bibliográficos
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
Descripción
Sumario: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.