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人乳头瘤病毒疫苗预防宫颈癌的最新进展。

Recent progress in vaccination against human papillomavirus-mediated cervical cancer.

机构信息

The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.

出版信息

Rev Med Virol. 2015 Mar;25 Suppl 1:54-71. doi: 10.1002/rmv.1824.

Abstract

It has been more than 7 years since the commercial introduction of highly successful vaccines protecting against high-risk human papillomavirus (HPV) subtypes and the development of cervical cancer. From an immune standpoint, the dependence of cervical cancer on viral infection has meant that HPV proteins can be targeted as strong tumour antigens leading to clearance of the infection and the subsequent protection from cancer. Commercially available vaccines consisting of the L1 capsid protein assembled as virus-like particles (VLPs) induce neutralising antibodies that deny access of the virus to cervical epithelial cells. While greater than 90% efficacy has been demonstrated at the completion of large phase III trials in young women, vaccine developers are now addressing broader issues such as efficacy in boys, longevity of the protection and inducing cross-reactive antibody for oncogenic, non-vaccine HPV strains. For women with existing HPV infection, the prophylactic vaccines provide little protection, and consequently, the need for therapeutic vaccines will continue into the future. Therapeutic vaccines targeting HPVE6 and E7 proteins are actively being pursued with new adjuvants and delivery vectors, combined with an improved knowledge of the tumour microenvironment, showing great promise. This review will focus on recent progress in prophylactic and therapeutic vaccine development and implementation since the publication of end of study data from phase III clinical trials between 2010 and 2012.

摘要

自高成功率的 HPV 疫苗(针对高危型 HPV 亚型)上市和宫颈癌疫苗研发以来,已经过去了 7 年多。从免疫角度来看,宫颈癌对病毒感染的依赖性意味着 HPV 蛋白可以作为强有力的肿瘤抗原进行靶向治疗,从而清除感染并随后预防癌症。由 L1 衣壳蛋白组装成病毒样颗粒(VLPs)的市售疫苗可诱导中和抗体,阻止病毒进入宫颈上皮细胞。虽然在对年轻女性进行的大型 III 期试验完成时已证明了大于 90%的疗效,但疫苗开发商现在正在解决更广泛的问题,例如在男孩中的疗效、保护的持久性以及诱导针对致癌、非疫苗型 HPV 株的交叉反应性抗体。对于已经存在 HPV 感染的女性,预防性疫苗提供的保护作用有限,因此,未来仍需要使用治疗性疫苗。目前正在积极研究针对 HPV E6 和 E7 蛋白的治疗性疫苗,采用了新的佐剂和递药载体,并结合对肿瘤微环境的深入了解,显示出巨大的潜力。本文将重点关注自 2010 年至 2012 年发表 III 期临床试验结束数据以来,预防性和治疗性疫苗研发和应用的最新进展。

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