1 Department of Pathology, Johns Hopkins Medical Institutions , Baltimore, Maryland.
2 Department of Oncology, Johns Hopkins Medical Institutions , Baltimore, Maryland.
Hum Gene Ther. 2018 Sep;29(9):971-996. doi: 10.1089/hum.2017.197. Epub 2018 Mar 16.
Human papillomavirus (HPV) has long been recognized as the causative agent of cervical cancer. High-risk HPV types 16 and 18 alone are responsible for over 70% of all cases of cervical cancers. More recently, HPV has been identified as an etiological factor for several other forms of cancers, including oropharyngeal, anogenital, and skin. Thus, the association of HPV with these malignancies creates an opportunity to control these HPV lesions and HPV-associated malignancies through immunization. Strategies to prevent or to therapeutically treat HPV infections have been developed and are still pushing innovative boundaries. Currently, commercial prophylactic HPV vaccines are widely available, but they are not able to control established infections or lesions. As a result, there is an urgent need for the development of therapeutic HPV vaccines, to treat existing infections, and to prevent the development of HPV-associated cancers. In particular, DNA vaccination has emerged as a promising form of therapeutic HPV vaccine. DNA vaccines have great potential for the treatment of HPV infections and HPV-associated cancers due to their safety, stability, simplicity of manufacturability, and ability to induce antigen-specific immunity. This review focuses on the current state of therapeutic HPV DNA vaccines, including results from recent and ongoing clinical trials, and outlines different strategies that have been employed to improve their potencies. The continued progress and improvements made in therapeutic HPV DNA vaccine development holds great potential for innovative ways to effectively treat HPV infections and HPV-associated diseases.
人乳头瘤病毒(HPV)长期以来被认为是宫颈癌的致病因子。高危型 HPV 16 和 18 单独就导致了超过 70%的宫颈癌病例。最近,HPV 被确定为几种其他形式癌症的病因因素,包括口咽癌、肛门生殖器癌和皮肤癌。因此,HPV 与这些恶性肿瘤的关联为通过免疫接种来控制这些 HPV 病变和 HPV 相关恶性肿瘤提供了机会。已经开发并仍在推动创新边界的预防或治疗 HPV 感染的策略。目前,商业预防性 HPV 疫苗广泛可用,但它们不能控制已建立的感染或病变。因此,迫切需要开发治疗性 HPV 疫苗,以治疗现有感染并预防 HPV 相关癌症的发生。特别是,DNA 疫苗已成为治疗性 HPV 疫苗的一种有前途的形式。由于其安全性、稳定性、制造简单性和诱导抗原特异性免疫的能力,DNA 疫苗在治疗 HPV 感染和 HPV 相关癌症方面具有巨大的潜力。本综述重点介绍了治疗性 HPV DNA 疫苗的现状,包括最近和正在进行的临床试验的结果,并概述了为提高其效力而采用的不同策略。治疗性 HPV DNA 疫苗开发方面的持续进展和改进为有效治疗 HPV 感染和 HPV 相关疾病提供了创新方法的巨大潜力。