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Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
Published on: March 8, 2012
Single-dose, therapeutic vaccination of mice with vesicular stomatitis virus expressing human papillomavirus type 16
John B Liao1, Jean Publicover, John K Rose
1Department 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.
Insights
Recombinant vesicular stomatitis virus (VSV) vaccines expressing the human papillomavirus (HPV) E7 oncogene effectively reduced tumor size in mice. This immunotherapy approach, dependent on CD8 T cells, shows promise for treating HPV-associated cancers.
Area of Science:
- Oncology
- Immunology
- Virology
- Vaccinology
Background:
- Recombinant vesicular stomatitis virus (VSV) is being developed as a vaccine vector for generating immune responses.
- Cancer immunotherapy offers a potential treatment strategy for human papillomavirus (HPV)-associated cancers, including cervical carcinoma.
- Targeting high-risk HPV lesions can induce cytotoxic T cells to eliminate viral antigen-expressing tumor cells.
Purpose of the Study:
- To explore the efficacy of VSV-based vaccines for cancer immunotherapy.
- To investigate the potential of VSV expressing the HPV16 E7 oncogene as a therapeutic vaccine against HPV-associated tumors.
Main Methods:
- Development of recombinant vesicular stomatitis virus (VSV) expressing the HPV type 16 (HPV16) E7 oncogene.
- Therapeutic vaccination of mice bearing TC-1 syngeneic tumors (which express HPV16 E7) with a single dose of the recombinant VSV-HPV16 E7 vaccine.
- Assessment of tumor volume changes and evaluation of the immune response, specifically the role of CD8 T cells.
Main Results:
- A single dose of VSV-HPV16 E7 vaccine generated HPV16 E7-specific T cells with cytotoxic activity against tumor cells.
- Vaccinated mice showed a 10-fold reduction in average tumor volume compared to control groups receiving empty-vector VSV.
- Regression of preexisting tumors was observed in some vaccinated mice, indicating a therapeutic effect.
- The observed antitumor effect was dependent on CD8 T cells.
Conclusions:
- Recombinant VSV-based vaccination can elicit antitumor responses against HPV16 E7.
- VSV vaccines expressing viral oncogenes represent a promising therapeutic strategy for cervical carcinoma and other HPV-associated cancers.
- Further exploration of VSV-based vaccination for HPV-associated malignancies is warranted.
