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Alireza Mohebbi, Sanaz Baghban Rahimi, Alijan Tabarraei, Mohsen Saeedi, Mirsaeed Ebrahimzadeh, Leila Alizadeh, Amir Ghaemi,
Volume 4, Issue 2 (10-2016)

Background and Objectives: Human papilloma virus (HPV) is known as the etiologic agent of cervical cancer and second common cancer among women. HPV viruses with the elevated risk of infection have more potentiality to cause cancer. The carcinogenesis in these viruses is accomplished by oncoproteins such as E7. Employing DNA vaccines which code specific antigens such as E7 is a novel therapeutic approach against such cancers.

Methods: In the present study, plasmid coding HPV16 E7 was administered intracutaneously to C57BL/6 tumoric mice models for investigation of its immunostimulating potential. PcDNA3.1+ vector was used as control vector. After immunization, spleen of animals were removed. Then, release of lactate dehydrogenase (LDH) was evaluated to address the cytotoxic activity (CTL) induced by cellular immunity in spleenocytes. Interferon-γ (IFN-γ) and interleukin-4 (IL-4) cytokines were also analyzed as profiles of Th1 and Th2, respectively. Anti-inflammatory cytokine interleukin-10 (IL-10) levels were also investigated in tumor microenvironments.

Results: Our results showed that CTL activity was higher among samples receiving HPV16 E7 coding vector in comparison to the group receiving pcDNA3.1+ control vector (P < 0.05). Levels of IFN-γ and IL-4 were also higher in the group receiving HPV16 E7 plasmid in comparison to the control group (P < 0.05). Similarly, IL-10 levels were significantly lower in tumor carrying mice groups receiving HPV16 DNA vaccine compare to PBS and pcDNA3.1 receiving control groups.

Conclusion: HPV16 E7 expressing DNA vaccine could increase the release of LDH due to immune system CTL activity. Elevation in IFN-γ and IL-4 levels as well as IL-10 reduction indicates an increase in both Th1 and Th2 profiles resulted by using potent DNA vaccine coding HPV16 E7 in tumor animal model.

Sanaz Baghbanrahimi, Hoorieh Soleimanjahi, Alireza Mohebbi, Mir Saeid Ebrahimzadeh, Leyla Alizade, Amir Ghaemi,
Volume 5, Issue 1 (5-2017)

Background & Objective: Human papillomavirus (HPV) oncoproteins, including E6 and E7 are constitutively expressed in cervical cancer cells. These proteins are ideal targets to be used for developing therapeutic vaccines against existing HPV-associated carcinomas. The aim of this study was to measure the proliferation response rate of splenic lymphocytes derived from E7-HPV16 encoding plasmid injection on the tumor mouse model of papillomavirus.
Method: C57BL/6 mice were inoculated subcutaneous with 5× 10⁵ TC-1 cells in three times with two weeks intervals and then immunized with HPV-16 E7 DNA vaccine. The proliferation response of splenic cells was measured by MTT assay. IL12 cytokine was measured by ELISA assay and the mass of tumor was calculated with caliper for six weeks.
Results: Following the application of DNA vaccines containing E7 therapeutic gene, the proliferative response of splenic cells was provoked significanltly higher than the stimulation in control group (P<0.05). Moreover, the secretion of IL12 was significantly increased in vaccinated mice tumor tissue (P<0.05). The growth of tumor in vaccinated group was markedly decreased in comparison to PBS and pcDNA3 groups (P<0.05).
Conclusion: Our findings revealed that the application of DNA vaccine containing E7 gene in a tumor mouse model may induce anti-tumor cellular immune responses.

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