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

Abstract

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.

• Authors: Byram W Bridle, Jeanette E Boudreau, Brian D Lichty, Jérôme Brunellière, Kyle Stephenson, Sandeep Koshy, Jonathan L Bramson, Yonghong Wan
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 17 Issue 10 Pg. 1814-21 (Oct 2009) ISSN: 1525-0024 [Electronic] United States
• PMID: 19603003 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Intramolecular Oxidoreductases
• dopachrome isomerase

Topics

• Adenoviridae (genetics)
• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (genetics, immunology, therapeutic use)
• Cell Line, Tumor
• Female
• Genetic Vectors (genetics)
• Humans
• Immunization, Secondary
• Intramolecular Oxidoreductases (genetics, immunology)
• Lung Neoplasms (complications, immunology, therapy)
• Melanoma (immunology, therapy)
• Mice
• Mice, Inbred C57BL
• T-Lymphocytes (immunology)
• Vesiculovirus (genetics)