Abstract | BACKGROUND:
Cervical cancer remains a leading cause of cancer-related mortality in women, particularly in developing countries. The causal association between genital human papilloma virus ( HPV) infection and cervical cancer has been firmly established, and the oncogenic potential of certain HPV types has been clearly demonstrated. Vaccines targeting the oncogenic proteins, E6 and E7 of HPV-16 and -18 are the focus of current vaccine development. Previous studies have shown that calreticulin (CRT) enhances the MHC class I presentation of linked peptide/ protein and may serve as an effective vaccination strategy for antigen-specific cancer treatment. METHODS: Two replication-deficient adenoviruses, one expressing HPV-16 E7 (Ad-E7) and the other expressing CRT linked to E7 (Ad-CRT/E7), were assessed for their ability to induce cellular immune response and tested for prophylactic and therapeutic effects in an E7-expressing mouse tumor model. RESULTS: Vaccination with Ad-CRT/E7 led to a dramatic increase in E7-specific T cell proliferation, interferon (IFN)-gamma-secretion, and cytotoxic activity. Immunization of mice with Ad-CRT/E7 was effective in preventing E7-expressing tumor growth, as well as eradicating established tumors with long-term immunological memory. CONCLUSION: Vaccination with an adenoviral vector expressing CRT-E7 fusion protein represents an effective strategy for immunotherapy of cervical cancer in rodents, with possible therapeutic potential in clinical settings.
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Authors | Jorge G Gomez-Gutierrez, Kutlu G Elpek, Roberto Montes de Oca-Luna, Haval Shirwan, H Sam Zhou, Kelly M McMasters |
Journal | Cancer immunology, immunotherapy : CII
(Cancer Immunol Immunother)
Vol. 56
Issue 7
Pg. 997-1007
(Jul 2007)
ISSN: 0340-7004 [Print] Germany |
PMID | 17146630
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Calreticulin
- Oncogene Proteins, Viral
- Papillomavirus E7 Proteins
- Papillomavirus Vaccines
- Recombinant Fusion Proteins
- oncogene protein E7, Human papillomavirus type 16
- Interferon-gamma
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Topics |
- Adenoviridae
- Animals
- Calreticulin
(genetics)
- Cell Proliferation
- Female
- Genetic Vectors
(genetics, immunology)
- Humans
- Interferon-gamma
(metabolism)
- Mice
- Mice, Inbred C57BL
- Microscopy, Confocal
- Oncogene Proteins, Viral
(genetics)
- Papillomavirus E7 Proteins
- Papillomavirus Infections
(immunology, prevention & control)
- Papillomavirus Vaccines
- Recombinant Fusion Proteins
(genetics, immunology)
- T-Lymphocytes
(immunology)
- Uterine Cervical Neoplasms
(immunology, prevention & control, virology)
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