National Taiwan University, Taipei, Taiwan.
BioDrugs. 2010 Apr 1;24(2):109-29. doi: 10.2165/11532810-000000000-00000.
The high-risk types of human papillomavirus (HPV) have been found to be associated with most cervical cancers and play an essential role in the pathogenesis of the disease. Despite recent advances in preventive HPV vaccine development, such preventive vaccines are unlikely to reduce the prevalence of HPV infections within the next few years, due to their cost and limited availability in developing countries. Furthermore, preventive HPV vaccines may not be capable of treating established HPV infections and HPV-associated lesions, which account for high morbidity and mortality worldwide. Thus, it is important to develop therapeutic HPV vaccines for the control of existing HPV infection and associated malignancies. Therapeutic vaccines are quite different from preventive vaccines in that they require the generation of cell-mediated immunity, particularly T cell-mediated immunity, instead of the generation of neutralizing antibodies. The HPV-encoded early proteins, the E6 and E7 oncoproteins, form ideal targets for therapeutic HPV vaccines, since they are consistently expressed in HPV-associated cervical cancer and its precursor lesions and thus play crucial roles in the generation and maintenance of HPV-associated disease. Our review covers the various therapeutic HPV vaccines for cervical cancer, including live vector-based, peptide or protein-based, nucleic acid-based, and cell-based vaccines targeting the HPV E6 and/or E7 antigens. Furthermore, we review the studies using therapeutic HPV vaccines in combination with other therapeutic modalities and review the latest clinical trials on therapeutic HPV vaccines.
人乳头瘤病毒（HPV）的高危型已被发现与大多数宫颈癌有关，并在疾病发病机制中发挥重要作用。尽管最近在预防性 HPV 疫苗开发方面取得了进展，但由于成本高和发展中国家供应有限，这些预防性疫苗在未来几年内不太可能降低 HPV 感染的流行率。此外，预防性 HPV 疫苗可能无法治疗已确立的 HPV 感染和 HPV 相关病变，这些病变在全球范围内造成高发病率和死亡率。因此，开发用于控制现有 HPV 感染和相关恶性肿瘤的治疗性 HPV 疫苗非常重要。治疗性疫苗与预防性疫苗有很大的不同，因为它们需要产生细胞介导的免疫，特别是 T 细胞介导的免疫，而不是产生中和抗体。HPV 编码的早期蛋白，E6 和 E7 癌蛋白，是治疗性 HPV 疫苗的理想靶标，因为它们在 HPV 相关宫颈癌及其前体病变中持续表达，因此在 HPV 相关疾病的发生和维持中发挥关键作用。我们的综述涵盖了各种治疗性 HPV 疫苗用于宫颈癌，包括基于活载体、肽或蛋白、核酸和基于细胞的疫苗，针对 HPV E6 和/或 E7 抗原。此外，我们还综述了使用治疗性 HPV 疫苗与其他治疗方式联合应用的研究，并综述了治疗性 HPV 疫苗的最新临床试验。
