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.
Highlights
Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a higher mortality rate than observers with melanoma, aging or immunosuppressed individuals are at increased risk of MCC1.Merkel cell polyomavirus (MCV) is the causative agent, which has been identified in 43–100% of MCC tumors[1,2]
A tumorigenicity study of CMS5-VP1 was performed as naïve BALB/c mice were inoculated with 1 × 106 of CMS5-VP1 or CMS5 cells subcutaneously to observe tumor growth (Supplementary Fig. 2d)
VP1-expressing in CMS5-VP1 and CMS5 tumor model were identified by Western blot (Supplementary Fig. 2e), cell lysate from CMS5-VP1 tumors demonstrated a specific VP1 band, and the band was absent in cell lysate from CMS5 tumor
Summary
Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a higher mortality rate than observers with melanoma, aging or immunosuppressed individuals are at increased risk of MCC1. Merkel cell polyomavirus (MCV) is the causative agent, which has been identified in 43–100% of MCC tumors[1,2]. Serological studies have indicated that MCV infection mainly occurs during early childhood, and the prevalence of MCV in the health population increases with age. This virus represents part of the skin microbiota in a latent, non-replicative state after infection[3,4,5]. The capsid proteins VP1, VP2, and VP3 are expressed after the onset of viral DNA replication to self-assemble into viral particles of ~55 nm diameter with icosahedral symmetry, VP1 is the major capsid protein to forming the viral particle and define the binding site required for infection, with the minor capsid protein VP2 may facilitate a post-attachment stage of MCV infectious, the role of VP3 in MCV infectious is still unclear[9,10]
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