Liao Shu-Jie, Deng Dong-Rui, Zeng Dan, Zhang Ling, Hu Xiao-Ji, Zhang Wei-Na, Li Li, Jiang Xue-Feng, Wang Chang-Yu, Zhou Jian-Feng, Wang Shi-Xuan, Zhang Han-Wang, Ma Ding
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Obstetrics and Gynaecology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, 430070, China.
J Huazhong Univ Sci Technolog Med Sci. 2013 Oct;33(5):735-742. doi: 10.1007/s11596-013-1189-5. Epub 2013 Oct 20.
Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide. Despite the encouraging development of the preventive vaccine for HPV, a vaccine for both prevention and therapy or pre-cancerous lesions remains in high priority. Thus far, most of the HPV therapeutic vaccines are focused on HPV E6 and E7 oncogene. However these vaccines could not completely eradicate the lesions. Recently, HPV E5, which is considered as an oncogene, is getting more and more attention. In this study, we predicted the epitopes of HPV16 E5 by bioinformatics as candidate peptide, then, evaluated the efficacy and chose an effective one to do the further test. To evaluate the effect of vaccine, rTC-1 (TC-1 cells infected by rAAV-HPV16E5) served as cell tumor model and rTC-1 loading mice as an ectopic tumor model. We prepared vaccine by muscle injection. The vaccine effects were determined by evaluating the function of tumor-specific T cells by cell proliferation assay and ELISPOT, calculating the tumor volume in mice and estimating the survival time of mice. Our in vitro and in vivo studies revealed that injection of E5 peptide+CpG resulted in strong cell-mediated immunity (CMI) and protected mice from tumor growth, meanwhile, prolonged the survival time after tumor cell loading. This study provides new insights into HPV16 E5 as a possible target on the therapeutic strategies about cervical cancer.
人乳头瘤病毒(HPV)引发的宫颈癌是全球女性中第二常见的癌症。尽管HPV预防性疫苗取得了令人鼓舞的进展,但开发一种兼具预防和治疗作用或针对癌前病变的疫苗仍然具有高度优先性。到目前为止,大多数HPV治疗性疫苗都聚焦于HPV E6和E7癌基因。然而,这些疫苗无法完全根除病变。最近,被视为癌基因的HPV E5受到越来越多的关注。在本研究中,我们通过生物信息学预测HPV16 E5的表位作为候选肽,然后评估其功效并选择一种有效的进行进一步测试。为评估疫苗效果,将rTC-1(被rAAV-HPV16E5感染的TC-1细胞)用作细胞肿瘤模型,将接种rTC-1的小鼠用作异位肿瘤模型。我们通过肌肉注射制备疫苗。通过细胞增殖试验和ELISPOT评估肿瘤特异性T细胞的功能、计算小鼠肿瘤体积并估计小鼠存活时间来确定疫苗效果。我们的体外和体内研究表明,注射E5肽+CpG可产生强大的细胞介导免疫(CMI),保护小鼠免受肿瘤生长,同时延长肿瘤细胞接种后的存活时间。本研究为HPV16 E5作为宫颈癌治疗策略的可能靶点提供了新见解。