Development of a therapeutic vaccine targeting Merkel cell polyomavirus capsid protein VP1 against Merkel cell carcinoma
Dan Xu, Sheng Jiang, Yue He, Xiang Jin, Gan Zhao, Bin Wang
Abstract
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.