Huang Chien-Fu, Monie Archana, Weng Wei-Hung, Wu Tc
Am J Transl Res. 2010 Jan 2;2(1):75-87.
Human papillomavirus (HPV), particularly type 16, has been associated with more than 99% of cervical cancers. There are two HPV oncogenic proteins, E6 and E7, which play a major role in the induction and maintenance of cellular transformation. Thus, immunotherapy targeting these proteins may be employed for the control of HPV-associated cervical lesions. Although the commercially available preventive HPV vaccines are highly efficient in preventing new HPV infection, they do not have therapeutic effects against established HPV infection or HPV-associated lesions. Since T cell-mediated immunity is important for treating established HPV infections and HPV-associated lesions, therapeutic HPV vaccine should aim at generating potent E6 and E7-specific T cell-mediated immune responses. DNA vaccines have now developed into a promising approach for antigen-specific T cell-mediated immunotherapy to combat infection and cancer. Because dendritic cells are the most potent professional antigen-presenting cells, and are highly effective in priming antigen-specific T cells, several DNA vaccines have employed innovative strategies to modify the properties of dendritic cells (DCs) for the enhancement of the DNA vaccine potency. These studies have revealed impressive pre-clinical data that has led to several ongoing HPV DNA vaccine clinical trials.
人乳头瘤病毒(HPV),尤其是16型,与99%以上的宫颈癌相关。有两种HPV致癌蛋白,即E6和E7,它们在细胞转化的诱导和维持中起主要作用。因此,针对这些蛋白的免疫疗法可用于控制HPV相关的宫颈病变。尽管市售的预防性HPV疫苗在预防新的HPV感染方面非常有效,但它们对已有的HPV感染或HPV相关病变没有治疗作用。由于T细胞介导的免疫对于治疗已有的HPV感染和HPV相关病变很重要,治疗性HPV疫苗应旨在产生有效的E6和E7特异性T细胞介导的免疫反应。DNA疫苗现已发展成为一种有前景的方法,用于抗原特异性T细胞介导的免疫疗法以对抗感染和癌症。因为树突状细胞是最有效的专职抗原呈递细胞,并且在启动抗原特异性T细胞方面非常有效,几种DNA疫苗采用了创新策略来改变树突状细胞(DC)的特性,以增强DNA疫苗的效力。这些研究已经揭示了令人印象深刻的临床前数据,这些数据导致了几项正在进行的HPV DNA疫苗临床试验。