Vesicular stomatitis virus as a novel cancer vaccine vector to prime antitumor immunity amenable to rapid boosting with adenovirus

Byram W. Bridle, Jeanette E. Boudreau, Brian D. Lichty, Jérôme Brunellière, Kyle Stephenson, Sandeep Koshy, Jonathan L. Bramson, Yonghong Wan

Résultat de recherche: Articleexamen par les pairs

97 Citations (Scopus)

Résumé

Vesicular stomatitis virus (VSV) has proven to be an effective vaccine vector for immunization against viral infection, but its potential to induce an immune response to a self-tumor antigen has not been investigated. We constructed a recombinant VSV expressing human dopachrome tautomerase (hDCT) and evaluated its immunogenicity in a murine melanoma model. Intranasal delivery of VSV-hDCT activated both CD4+ and CD8+ DCT-specific T-cell responses. The magnitude of these responses could be significantly increased by booster immunization with recombinant adenovirus (Ad)-hDCT, which led to enhanced efficacy against B16-F10 melanoma in both prophylactic and therapeutic settings. Notably, the interval of VSV/Ad heterologous vaccination could be shortened to as few as 4 days, making it a potential regimen to rapidly expand antigen-specific effector cells. Furthermore, VSV-hDCT could increase DCT-specific T-cell responses primed by Ad-hDCT, suggesting VSV is efficient for both priming and boosting of the immune response against a self-tumor antigen.

Langue d'origineEnglish
Pages (de-à)1814-1821
Nombre de pages8
JournalMolecular Therapy
Volume17
Numéro de publication10
DOI
Statut de publicationPublished - 2009
Publié à l'externeOui

Note bibliographique

Funding Information:
We thank Mary-Jo Smith and Mary Bruni for assistance with immunohistochemical staining; Xueya Feng, Duncan Chong, and Natasha Kazdhan for technical assistance with virus preparation. This work was supported by grants to Y.W. from the Canadian Institutes of Health Research [MOP-67066] and the Ontario Cancer Research Network. J.E.B. is supported by studentships from the Natural Sciences and Engineering Research Council. We have no financial conflicts of interest related to this research.

ASJC Scopus Subject Areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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