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Original Articles
Immunization with Adenoviral Vectors Carrying Recombinant IL-12 and E7 Enhanced the Antitumor Immunity against Human Papillomavirus 16-associated Tumor
Eun-Kyung Park, Young-Wook Kim, Joon-Mo Lee, Sung-Eun NamKoong, Do-Gang Kim, Heung-Jae Chun, Byoung-Don Han, Su-Mi Bae, Hyun-Sun Jin, Jeong-Im Sin, Woong-Shick Ahn
Cancer Res Treat. 2005;37(1):63-70.   Published online February 28, 2005
DOI: https://doi.org/10.4143/crt.2005.37.1.63
AbstractAbstract PDFPubReaderePub
Purpose

Human papillomavirus (HPV) infection has a significant role in cervical carcinogenesis, and HPV oncoprotein E7 plays an important part in the formation and maintenance of cervical cancer. Interleukin-12 (IL-12) has been reported to induce a cellular immune response, and to suppress the tumor growth and the E7 production. Here we describe the use of adenoviral delivery of the HPV 16 E7 subunit (AdE7) along with adenoviral delivery of IL-12 (AdIL-12) in mice with HPV-associated tumors.

Materials and Methods

Mice were injected with TC-1 cells to establish TC-1 tumor, and then they were immunized with AdIL-12 and/or AdE7 intratumorally. The anti tumor effects induced by AdIL-12 and/or E7 were evaluated by measuring the size of the tumor. E7-specific antibody and INF-γ production in sera, and the T-helper cell proliferative responses were then measured. Cytotoxic T-lymphocyte (CTL) and T cell subset depletion studies were also performed.

Results

Combined AdIL-12 and AdE7 infection at the tumor sites significantly enhanced the antitumor effects more than that of AdIL-12 or AdE7 single infection. This combined infection resulted in regression of the 9 mm sized tumors in 80% of animals as compare to the PBS group. E7-specific antibody and INF-γ production in the sera, and the T-helper cell proliferative responses were significantly higher with coinfection of AdIL-12 and AdE7 than with AdIL-12 or AdE7 alone. CTL response induced by AdIL-12 and AdE7 in the coinjected group suggested that tumor suppression was mediated by mostly CD8+ and only a little by the CD4+ T cells.

Conclusion

IL-12 and E7 application using adenovirus vector showed antitumor immunity effects against TC-1 tumor, and this system could be use in clinical applications for HPV-associated cancer. (ED note: nice abstract.)

Citations

Citations to this article as recorded by  
  • Development of a replication‐deficient adenoviral vector‐based vaccine candidate for the interception of HPV16‐ and HPV18‐induced infections and disease
    Selina Khan, Koen Oosterhuis, Kerstin Wunderlich, Evelien M. Bunnik, Melissa Bhaggoe, Satish Boedhoe, Santusha Karia, Renske D.M. Steenbergen, Leontien Bosch, Jan Serroyen, Sarah Janssen, Hanneke Schuitemaker, Jort Vellinga, Gert Scheper, Roland Zahn, Jer
    International Journal of Cancer.2017; 141(2): 393.     CrossRef
  • Immune responses and protective efficacy of a recombinant swinepox virus expressing HA1 against swine H1N1 influenza virus in mice and pigs
    Jiarong Xu, Dongyan Huang, shichao Liu, Huixing Lin, Haodan Zhu, Bao Liu, Chengping Lu
    Vaccine.2012; 30(20): 3119.     CrossRef
  • Immune responses and protection efficacy of a recombinant swinepox virus expressing HA1 against swine H3N2 influenza virus in mice and pigs
    Jiarong Xu, Dongyan Huang, Shichao Liu, Huixing Lin, Haodan Zhu, Bao Liu, Chengping Lu
    Virus Research.2012; 167(2): 188.     CrossRef
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Polymorphisms in E6 Gene of Human Papillomavirus Type 16 Found in Cervical Tissues from Korean Women
Jae Weon Kim, Ju Won Roh, Moon Hong Kim, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee
J Korean Cancer Assoc. 2000;32(5):875-883.
AbstractAbstract PDF
PURPOSE
To examine the distribution of HPV 16 E6 polymorphisms and analyse the possible association between the polymorphisms and cervical cancer development in Korean women.
MATERIALS AND METHODS
Fifty-four cases of uterine cervical tissues containing HPV 16 DNA confirmed by polymerase chain reaction (PCR) from Korean women were subjected to investigate the E6 gene mutations. PCR-amplified products were sequenced by the fluorescent dideoxy ter mination method and the results obtained from sequencing were analysed. And newly designed PASA method was tried to develop rapid test for identification of the most commonly detected variation.
RESULTS
Among the 27 cervical cancer cases, only two (7.4%) was found as a prototype. Among 11 kind of variants identified in total, 4 variants (5 nucleotide sites) which were never reported before has been found, registered firstly to GenBank. The most frequently found variation was D25E, absolutely different from the previous reports from the western country. There was no statistically significant trend for the D25E variation to be more frequently detected in cancerous lesions than in noncancerous lesions. All of the DNA sequencing results observed could be confirmed by PASA method.
CONCLUSION
These results suggest that Korean-specific genetic factors might operate during the cervical carcinogenesis.
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Comparison of HPV 16 Sequence Variations at Upstream Regulatory Region in the Couples of Patients with Cervical Cancer for Determination of HPV Infectivity
Jae Weon Kim, Yong Sang Song, Hye Won Jeon, No Hyun Park, Soon Beom Kang, Hyo Pyo Lee
J Korean Cancer Assoc. 1999;31(2):403-410.
AbstractAbstract PDF
PURPOSE
Although it is now generally accepted that human papillomaviruses (HPVs) are causally related to cervical neoplasia by plentiful epidemioiogic and experimental works, little is known about the direct evidence of sexual transmission of HPV. This study was undertaken to confirm the transmission route and determine the infectivity of HPV by comparison of HPV 16 sequence variations at upstream regulatory region (URR) in the couples of patient with cervical cancer.
MATERIALS AND METHODS
HPV DNAs obtained from genital lesions of forty married couples of patients with cervical cancer were evaluated by polymerase chain reaction (PCR) and PCR-directed sequencing.
RESULTS
HPV 16 was detected in fourteen (63.6%) of twenty-two male consorts whose wives were positive for HPV 16. Of these, six (42.9%) couples demonstrated identical HPV 16 URR variants between patients and male consorts, and eight had mismatching HPV 16 URR sequences. Among six couples showed matching HPV 16 variants, three couples mamed for 10, 19, 25 years respectively carried variant 7728/7779, two couples married for 15 years each carried variant 7728/7762, and one couple married for 18 years carried variant 7728/7797, CONCLUSION: These data suggest that sexual transmission of HPV 16 does occur. A search for more HPV variants in a large cohort is needed to secure high level of precision in molecular epidemiologic study using HPV variant.
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Change of the Antigenecity of Human Papillomavirus Type 16 E7 Oncoprotein according to Phosphorylation
No Hyun Park, Sun Ho Kee, Joo Won Noh, Jae Weon Kim, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee
J Korean Cancer Assoc. 1998;30(2):313-320.
AbstractAbstract PDF
PURPOSE
It was suggested that immunogenic region of E7 proteins of human papillo- mavirus (HPV) type 16 encompass casein kinase (CK) II phosphorylation site and the resulting negative charge may affect the various biologic function of E7 protein. This study was undertaken to analyze the change of antigenic characteristics of HPV type 16, E7 oncoprotein according to phosphorylation.
MATERIALS AND METHODS
We produced two monoclonal antibodies (VD6 and IB10) which showed different reactivities to E7 proteins expressed from bacteria or extracted from CaSki cell. These reaction were analyzed by Western blotting. Also the antigenic sites estimation of these antibodies using nested deletion sets was done. On the basis of above experiments, we performed in vitro phosphorylation assay using CK II and its specific inhibitor, DRB (5, 6-dichloro-l-beta-D-ribofuranosylbenzimidazole), to analyze the IB10 reactivity to E7 oncoproteins according to phosphorylation.
RESULTS
In Westem blot analysis, VD6 and IB10 antibodies reacted strongly to bacterially expressed E7 protein. But using E7 extracted from CaSki cell, VD6 reacted to 2.0 kDa E7 protein whereas IB10 showed weak reactivity. The antigenic sites estimation of these antibodies showed that antigenic site of VD6 was located in amino terminal region and that of IB10 in the middle portion in the range of approximate amino acid 25-45. The antigenic site of IB10 might contain the possible phosphorylation sites (Ser-31, 32) in E7. Considering this, the different reactivities of IB10 to E7 proteins expressed in bacteria and extracted from CaSki cell might be due to phosphorylation. In in vitro phosphorylation assay using CK II, the phosphorylation of E7 increased according to reaction time. And this phosphorylation reduced the reactivity of IB10 to E7 protein whereas the reactivity of VD6 did not change. Also the reactivity of IB10 to E7 protein increased in a dose dependent manner with CK II specific inhibitor, DRB treated CaSki cell extracts.
CONCLUSION
These result showed the antigenecity is affected by the degree of phosphorylation of E7 protein.
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