Browse > Article
http://dx.doi.org/10.7314/APJCP.2015.16.9.3843

Immunotherapeutic Effects of Dendritic Cells Pulsed with a Coden-optimized HPV 16 E6 and E7 Fusion Gene in Vivo and in Vitro  

Zhou, Zhi-Xiang (College of Life Science and Bioengineering, Beijing University of Technology)
Li, Dan (College of Life Science and Bioengineering, Beijing University of Technology)
Guan, Shan-Shan (College of Life Science and Bioengineering, Beijing University of Technology)
Zhao, Chen (College of Life Science and Bioengineering, Beijing University of Technology)
Li, Ze-Lin (College of Life Science and Bioengineering, Beijing University of Technology)
Zeng, Yi (College of Life Science and Bioengineering, Beijing University of Technology)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.9, 2015 , pp. 3843-3847 More about this Journal
Abstract
Background: Cervical cancer is the second most common cause of cancer related death of women. Persistent HPV infection, especially with high-risk types such as HPV16 and HPV18, has been identified to be the primary cause of cervical cancer. E6 and E7 are the major oncoproteins of high-risk HPVs, which are expressed exclusively in HPV infected tissues, and thereby represent ideal therapeutic targets for immunotherapy of cervical cancer. Materials and Methods: In this work, we used recombinant adenovirus expressing coden-optimized HPV16 E6 and E7 fusion protein (Ad-ofE6E7) to prime dendritic cells (DC-ofE6E7), to investigate the ability of primed DC vaccine in eliciting antitumor immunity in vitro and vivo. Results: Our results indicated that DC-ofE6E7 vaccine co-culturing with splenocytes could strongly induce a tumor-specific cytotoxic T lymphocyte (CTL) response and kill the TC-1 cells effectively in vitro. Moreover, DC-ofE6E7 vaccine induced protective immunity against the challenge of TC-1 cancer cells in vivo. Conclusions: The results suggested that the HPV16 ofE6E7 primed DC vaccine has potential application for cervical cancer immunotherapy.
Keywords
Human papillomavirus 16; E6; E7; dendritic cells; vaccine; cervical cancer;
Citations & Related Records
Times Cited By KSCI : 4  (Citation Analysis)
연도 인용수 순위
1 Aggarwal P (2014). Cervical cancer: can it be prevented? World J Clin Oncol, 5, 775-80.   DOI
2 Bellone S, Pecorelli S, Cannon MJ, et al (2007). Advances in dendritic cell-based therapeutic vaccines for cervical cancer. Expert Rev Anticancer Ther, 7, 1473-86.   DOI   ScienceOn
3 Chansaenroj J, Theamboonlers A, et al (2012). Whole genome analysis of human papillomavirus type 16 multiple infection in cervical cancer patients. Asian Pac J Cancer Prev, 13, 599-606.   DOI   ScienceOn
4 Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.   DOI
5 Jiang P, Yue Y (2014). Human papillomavirus oncoproteins and apoptosis (Review). Exp Ther Med, 7, 3-7.
6 Kozlowska A, Mackiewicz J, Mackiewicz A (2013). Therapeutic gene modified cell based cancer vaccines. Gene, 525, 200-7.   DOI
7 Lutz MB, Kukutsch N, Ogilvie ALJ, et al (1999). An advanced culture method for generating large quantities of highly pure Dendritic cells from mouse Bone Marrow. J Immunol Methods, 223, 77-92.   DOI
8 Meixlsperger S, Leung CS, Ramer PC, et al (2013). CD141+ dendritic cells produce prominent amounts of IFN-${\alpha}$ after dsRNA recognition and can be targeted via DEC-205 in humanized mice. Blood, 121, 5034-44.   DOI
9 Mellman I, Steinman RM (2001). Dendritic cells: specialized and regulated antigen processing machines. Cell, 106, 255-8.   DOI
10 Nakagawa S, Wantanabe S, Yoshikawa H, et al (1995). Mutational analysis of human papillomavirus type 16 E6 protein: transforming function for human cells and degradation of P53 in vitro. Virology, 212, 535-42.   DOI
11 Ohlschlager P, Quetting M, Alvarez G, et al (2009). Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequenceoptimized genetic adjuvants. Int J Cancer, 125, 189-98.   DOI
12 Palucka K, and Banchereau J (2012). Cancer immunotherapy via dendritic cells. Nat Rev Cancer, 12, 265-77.   DOI
13 Ramanathan P, Ganeshrajah S, Raghanvan R (2014). Development and clinical evaluation of dendritic cell vaccines for HPV related cervical cancer-a feasibility study. Asian Pac J Cancer Prev, 15, 5909-16.   DOI
14 Schlitzer A, McGovern N, Teo P, et al (2013). IRF4 Transcription factor-dependent CD11b (+) Dendritic cells in Human and mouse control Mucosal IL-17 Cytokine responses. Immunity, 38, 970-83.   DOI   ScienceOn
15 Seo SH, Jin HT, Park SH, et al (2009). Optimal induction of Hpv DNA vaccine-induced CD8+ T cell responses and therapeutic antitumor effect by antigen engineering and electroporation. Vaccine, 27, 5906-12.   DOI
16 Tanchot C, Terme M, Pere H, Tran, T, et al (2013). Tumorinfiltrating regulatory T cells: phenotype, role, mechanism of expansion in situ and clinical significance. Cancer Microenviron, 6, 147-57.   DOI
17 Tran N, Hung C, Roden R, Wu T (2014). Control of HPV infection and related cancer through vaccination. Recent Results Cancer Res, 193, 149-71.   DOI
18 Wu X, Liu X, Jiao Q (2014). Cytotoxic T Lymphocytes elicited by dendritic cell-targeted delivery of human papillomavirus type-16 E6/E7 fusion gene exert lethal effects on CaSki cells. Asian Pac J Cancer Prev, 15, 2447-51.   DOI
19 Xie Q, Zhou Z, Li Z, Zeng Y (2011). Transforming activity of a novel mutant of HPV16 E6E7 fusion gene. Virol Sin, 26, 206-13   DOI
20 Yan J, Reichenbach DK, Corbitt N, et al (2009). Induction of antitumor immunity in vivo following delivery of a novel Hpv-16 DNA vaccine encoding an E6/E7 fusion antigen. Vaccine, 27, 431-40.   DOI
21 Zhou Z, Zhao C, Li Q, Zeng Y (2014). A novel mutant of Human Papillomavirus Type 18 E6E7 fusion gene and its transforming activity. Asian Pac J Cancer Prev, 15, 7395-9.   DOI