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Korean Journal of Obstetrics & Gynecology 2003;46(12):2373-2379.
Published online December 1, 2003.
Induction of Anti-tumor Immunity by Vaccination with E7 of HPV16 and IL-12.
Eun Kyung Park, Tae Young Jin, Chul Gu Yoon, Mi Nah Choi, Seung Won Huh, Su Mi Bae, Young Wan Kim, Joo Hee Yoon, Woong Shick Ahn, Chong Kook Kim, Jun Mo Lee, Sung Eun Namkoong, Kim Dou Kang
1Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea.
2Catholic Research Institutes of Medical Science, College of Medicine, The Catholic University of Korea.
3College of Pharmacy, Seoul National University, Korea.
Abstract
OBJECTIVE
Interleukin-12 is well known to induce cellular immune response materials and suppress the tumor growth. HPV infection has significant roles in cervical carcinogenesis, and HPV oncoprotein E6 and E7 are important roles in formation and maintenance of cervical cancer. E7 specific immune response was detected in cervical cancer patients, and this shows that E7 protein would be important in potential immunetherapy in cervical cancer. This study is aimed to investigate antitumor effect and E7 immune response by injection of adenovirus IL-12 and E7 in cervical cancer animal model. METHODS: In the cervical cancer animal model using C57BL/6 mice and HPV16 E7 immortalized hosts, 5 X 10(8) pfu/100 ul of PBS, AdLacZ, AdE7 and AdIL-12 were injected into the tumor mass when the tumor sized is increased to 7-8 mm. After the injection, the tumor size was caliperated every 2-3 days, and pathologic and blood studies were done on day 1, 3, 5, 7, 11, 12, and 21 days. The expression level of IL-12 and INF- and E7 specific immune response were measured by ELISA. RESULTS: After the injection of AdIL-12 into the tumor mass, 45% of tumor growth suppression was noted in comparison with control group. In the cases of combination injections of AdIL-12 and AdE7, 80% growth suppression was observed, and complete regression was shown in 40% of the study group. After injection of AdIL-12, the expression of IL-12 in the tumor mass was 9 time higher than that of control group, and 6 times higher in blood sample in comparison with control group. In the group with combined AdIL-12 and AdE7, the highest expression of INF- was noted in comparison with single injection of AdIL-12 or control group. IgGI and IgG2b isotype expression level increased 2.5 times and 2.2 times respectively 3 weeks after adenovirus injection. CONCLUSION: In cervical cancer animal model, IL-12 and E7 application using Adenovirus vector is significant antitumor effect and this demonstrates the potential immunotherapy in near future.
Key Words: Cervical cancer animal model, Adenovirus IL-12 and E7, Antitumor effect
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