Golestan University of Medical Sciences Repository

DNA vaccine encoding HPV-16 E7 with mutation in L-Y-C-Y-E pRb-binding motif induces potent anti-tumor responses in mice

Bahrami, A.A. and Ghaemi, A. and Tabarraei, A. and Sajadian, A. and Gorji, A. and Soleimanjahi, H. (2014) DNA vaccine encoding HPV-16 E7 with mutation in L-Y-C-Y-E pRb-binding motif induces potent anti-tumor responses in mice. Journal of Virological Methods, 206. pp. 12-18. ISSN 01660934 (ISSN)

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Abstract

Cervical cancer is the second most common cancer among women worldwide and remains a clinical problem despite improvements in early detection and therapy. The human papillomavirus (HPV) type 16 (HPV16) E7 oncoprotein expressed in cervical carcinoma cells are considered as attractive tumor-specific antigen targets for immunotherapy. Since the transformation potential of the oncogenes, vaccination based of these oncogenes is not safe. In present study, DNA vaccine expressing the modified variant with mutation in pRb-binding motif of the HPV-16 E7 oncoprotein was generated. A novel modified E7 gene with mutation in LYCYE motif was designed and constructed and the immunogenicity and antitumor effect of therapeutic DNA vaccines encoding the mutant and wild type of E7 gene were investigated. The L-Y-C-Y-E pRb-binding motif of E7 proteins has been involved in the immortalization and transformation of the host cell. The results showed that the mutant and wild type HPV-16 E7 vectors expressed the desired protein. Furthermore, the immunological mechanism behind mutant E7 DNA vaccine can be attributed at least partially to increased cytotoxic T lymphocyte, accompanied by the up-regulation of Th1-cytokine IFN-γ and TNF-β and down-regulation of Th3-cytokine TGF-β. Immunized mice with mutant plasmid demonstrated significantly stronger cell immune responses and higher levels of tumor protection than wild-type E7 DNA vaccine. The results exhibit that modified E7 DNA vaccine may be a promising candidate for development of therapeutic vaccine against HPV-16 cancers. © 2014 Elsevier B.V.

Item Type: Article
Additional Information: Unmapped bibliographic data: LA - English [Field not mapped to EPrints] J2 - J. Virol. Methods [Field not mapped to EPrints] AD - Department of Medical Biotechnology, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran [Field not mapped to EPrints] AD - Department of Microbiology, Golestan University of Medical Sciences, Gorgan, Iran [Field not mapped to EPrints] AD - Shefa Neuroscience Research Center, Tehran, Iran [Field not mapped to EPrints] AD - Institut für Physiologie I, Westfälische Wilhelms-Universität Münster, Robert-Koch-Strasse Münster, Germany [Field not mapped to EPrints] AD - Klinik und Poliklinik für Neurochirurgie, Westfälische Wilhelms-Universität Münster, Münster, Germany [Field not mapped to EPrints] AD - Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran [Field not mapped to EPrints] DB - Scopus [Field not mapped to EPrints]
Uncontrolled Keywords: Cervical cancer, DNA vaccines, E7, Human papilloma virus, Mutant, PRb-binding motif, cysteine, DNA vaccine, gamma interferon, glutamic acid, interleukin 4, leucine, lymphotoxin, protein E7, retinoblastoma protein, transforming growth factor beta, tumor necrosis factor alpha, tyrosine, Wart virus vaccine, animal cell, animal experiment, animal model, antineoplastic activity, article, binding site, cell immortalization, cell transformation, cellular immunity, controlled study, cytotoxic T lymphocyte, down regulation, drug design, E7 gene, female, gene, gene mutation, Human papillomavirus type 16, immunogenicity, mouse, nonhuman, priority journal, protein expression, protein structure, upregulation, uterine cervix cancer, vaccine production, viral gene therapy
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
موارد کلی
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 19 Apr 2015 05:17
Last Modified: 04 May 2015 07:49
URI: http://eprints.goums.ac.ir/id/eprint/1683

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