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Clin Vaccine Immunol. 2008 May;15(5):817-24. doi: 10.1128/CVI.00343-07. Epub 2008 Mar 12.

Single-dose, therapeutic vaccination of mice with vesicular stomatitis virus expressing human papillomavirus type 16 E7 protein.

Author information

1
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.

Abstract

We are developing recombinant attenuated vesicular stomatitis virus (VSV) as a vaccine vector to generate humoral and cell-mediated immune responses. Here, we explore the use of VSV vaccines for cancer immunotherapy. Immunotherapy targeting high-risk human papillomavirus (HPV) lesions has the potential to benefit HPV-infected individuals and cervical cancer patients by generating cytotoxic T cells that kill tumor cells that express viral antigens. A single dose of VSV expressing the HPV type 16 (HPV16) E7 oncogene was used for therapeutic vaccination of mice bearing TC-1 syngeneic tumors, which express HPV16 E7. HPV16 E7-specific T cells were generated and displayed cytotoxic activity against the tumor cells. By 14 days postvaccination, average tumor volumes were 10-fold less in the vaccinated group than in mice that received the empty-vector VSV, and regression of preexisting tumors occurred in some cases. This antitumor effect was CD8 T-cell dependent. Our results demonstrate antitumor responses to HPV16 E7 and suggest that recombinant-VSV-based vaccination should be explored as a therapeutic strategy for cervical carcinoma and other HPV-associated cancers.

PMID:
18337377
PMCID:
PMC2394842
DOI:
10.1128/CVI.00343-07
[Indexed for MEDLINE]
Free PMC Article

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