Recombinant bacteria vector and virus vector expressing human papillomavirus E7 gene as the tumor vaccine for cervical carcinoma and its metastasis

• Main Authors: Jen-Yi Lee, 李仁譯
• Other Authors: Show-Li Chen
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/27882820885615537555

碩士 === 國防醫學院 === 微生物及免疫學研究所 === 88 === In 1998, cervical cancer is the fourth death rate of carcinoma from the statistical report of the Department of Health of the Executive Yuan in Taiwan. It’s the fifth according to the newly report in 1999. The major cause of cervical cancer is human papilloma virus (HPV) type 16 and 18. The oncogenes of HPV are E5, E6 and E7. Among them, the expression of E7 oncogene has correlation with the cervical carcinoma. In present, there’re several tumor vaccines that were developed in the light of E7, and each of them has its different efficacy. Listeria monocytogenes (LM) is a Gram positive, facultative intracellular bacterium. It infects the host cells by phagocytosis, and then secrets the listeriolysin O to destroy the phagosome. LM can induce the cellular immune response through MHC class I and class II pathways in cytoplasm. We have constructed the recombinant LM expressing HPV-16 E7 gene by genetic engineering, and improved that it can induce the CTL immune response by I.V. injection in animal model. Beside, the CTL immune response and the protective of host can be induced by oral administration. The recombinant adeno-associated virus (rAAV) expressing HPV-16 E7CTL epitope fused heat shock proteins (E7CTL-hsp), which based on the latest study in our lab was make use of metastasis research. Metastasis is frequently cause death in cancer patients. It cannot completely control the occurrence of metastasis in clinical treatment. In this study, we use the I.V. injection of TC-1 cells as lung metastasis model and estimate the vaccine efficacy of rAAV E7CTL-hsp. The result indicate that rAAV E7CTL-hsp can induced the CTL immune response and the numbers of pulnamory nodule was significantly reduced in lung. The apoptotic body and lymphocyte filtration were found in lung tissue section by pathological examination. Our study showed the rAAV E7CTL-hsp has not only the clearance efficacy to the primary tumor but also the inhibition of metastasis.