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

针对默克尔细胞多瘤病毒衣壳蛋白VP1的治疗性疫苗的研发,以对抗默克尔细胞癌

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Abstract

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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