DNA Vaccines against Hamster Oral Papillomavirus Associated Oral Cancer

在以前的研究中，我们开发了一个高度可重复的致癌模型相结合的DMBA应用与仓鼠舌粘膜的物理创伤。利用该动物模型，我们通过对该病毒基因组的分子克隆和测序证实了一种新的仓鼠口腔乳头瘤病毒（HOPV）的存在。在本研究中，我们使用该HOPV仓鼠模型来测试单独接种L1、E6或E7基因以及pDNA/mBSA复合物是否可以预防口腔癌的发生。E6或E7基因、pDNA/mBSA或仅载体分别起始于仓鼠。用DMBA涂抹仓鼠舌尖，每周3次，共8周。然后在麻醉下切除舌尖的中间部分，纵向厚度为2 mm。此后，每天用DMBA涂抹尖端直到动物被处死。所有载体注射的仓鼠都显示舌癌。在单独的基因和L1、E6和E7接种的仓鼠的pDNA/mBSA复合物中观察到癌症发展的一些延迟。结果表明，L1、E6和E7 DNA疫苗免疫后，可延缓乳头瘤病毒相关性口腔癌的发生发展，而电化学疗法可使L1基因疫苗的抗肿瘤作用增强。

In a previous investigation, we developed a highly reproducible carcinogenesis model by combining DMBA application with physical wounding of the hamster lingual mucosa. Using this animal model, we demonstrated the presence of a novel hamster oral papillomavirus (HOPV) by the molecular cloning and sequencing of this viral genome.In this study, we used this HOPV hamster model to test whether vaccination with either the L1, E6 or E7 genes alone and pDNA/mBSA complex could prevent oral carcinoma development.An immunization protocol using intramuscular injection of DNA plasmids encoding the L1, E6 or the E7 gene, pDNA/mBSA or vector only, respectively was initiated to hamsters. The lingual tips of hamsters were painted three times a week with DMBA for 8 weeks. The middle portion of the lingual tip, 2 mm in longitudinal thickness, was then excised under anaesthesia. Thereafter, the tips were painted daily with DMBA until the animals were sacrificed.The all vector-injected hamsters showed lingual carcinoma. Some delay in cancer development in both of genes alone and pDNA/mBSA complex of the L1, E6 and E7-vaccinated hamsters was observed. In particular, L1 pDNA/mBSA complex vaccinated hamsters showed no lesions.Using the electrochemotherapy, anti-cancer effects were enhanced in L1 gene vaccine.These results suggested that immunization with L1, E6 and E7 DNA vaccines delayed carcinoma development of papillomavirus-associated oral cancer and electrochemotherapy is very useful technique for the insert DNA vaccines to the cells of tissues.