Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research.
Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research.
复制标题
DOI：
10.3802/jgo.2016.27.e51
复制
发表时间：
2016-09
影响因子：
3.9
通讯作者：
Hung CF
中科院分区：
文献类型：
--
作者：
Lee SJ;Yang A;Wu TC;Hung CF
宫颈癌是世界上第四大致命的女性癌症。目前针对宫颈癌的治疗包括手术、放疗、化疗和抗血管生成剂。然而，尽管用于治疗宫颈癌的各种治疗方法，其疾病负担仍然是一个全球性问题。人乳头瘤病毒（human papillomavirus，HPV）的持续感染是宫颈癌等多种癌症发病的重要环节，在全球范围内开展了全国性的HPV筛查和预防性HPV疫苗接种计划。然而，即使市售的预防性HPV疫苗Gardasil（Merck）和Cervarix（GlaxoSmithKline）通过产生HPV特异性中和抗体有效阻断HPV进入宫颈上皮，它们也不能消除预先存在的HPV感染。出于这些原因，针对HPV相关疾病的其他免疫选择，包括治疗性疫苗，一直在不断探索。治疗性HPV疫苗通过主要调节树突状细胞和细胞毒性T淋巴细胞来增强靶向HPV E6和E7抗原的细胞介导的免疫。我们的综述将涵盖正在开发的用于治疗HPV相关病变和癌症的各种治疗性疫苗。此外，我们还将讨论免疫检查点抑制剂的潜力，这些抑制剂最近已被采用并测试了其对HPV诱导的宫颈癌的治疗效果。
Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.