Cervical cancer is a major public health problem and one of the leading causes of cancer deaths in women. Virtually all cases of cervical cancer, as well as a growing share of anal and head/neck tumors, are associated with human papillomavirus (HPV) infection. Despite the effectiveness, the available prophylactic vaccines do not benefit women with cervical lesions or cancer. Therefore, the search of new immunotherapeutic approaches to treat HPV-induced tumors is still a priority. The present study characterizes a therapeutic antitumor vaccine based on the genetic fusion of the Herpes simplex virus-1 (HSV-1) glycoprotein D (gD) with the E7 oncoprotein from HPV-16 (gDE7). Two subcutaneous doses of gDE7, admixed with poly (I:C), conferred complete and long-lasting therapeutic antitumor protection on mice previously challenged with tumor cells expressing the HPV-16 oncoproteins. The vaccine induced multifunctional E7-specific CD8+ T cells with cytotoxic activity and effector memory phenotype (CD44+ CD62Llow). In addition, gDE7 admixed with poly (I:C) vaccination controlled the expansion of tumor-induced regulatory T cells and myeloid-derived suppressor cells. More importantly, gDE7 activated mouse CD11c+ CD8α+ and human BDCA3+ dendritic cells (DC), specialized in antigen cross-presentation to CD8+ T cells, under in vitro conditions. These results indicated that the activation of a specific DC population, mediated by gD, improved the antigen-specific immune responses and the therapeutic performance induced by antitumor vaccines. These results open perspectives for the clinical testing of gDE7-based vaccines under the concept of active immunization as a tool for the therapeutic control of cancer. Mol Cancer Ther; 16(9); 1922–33. ©2017 AACR .

中文翻译：

---

单纯疱疹病毒糖蛋白D靶向特定的树突状细胞亚群，并提高针对人乳头瘤病毒相关肿瘤的疫苗的性能。

宫颈癌是一个重大的公共卫生问题，也是女性癌症死亡的主要原因之一。几乎所有子宫颈癌病例以及越来越多的肛门和头颈肿瘤病例都与人乳头瘤病毒（HPV）感染有关。尽管有效果，但是可用的预防性疫苗并没有使患有宫颈病变或癌症的妇女受益。因此，寻找新的免疫治疗方法来治疗HPV诱导的肿瘤仍然是一个优先事项。本研究的特征是基于单纯疱疹病毒1（HSV-1）糖蛋白D（gD）与HPV-16的E7癌蛋白（gDE7）的遗传融合来表征治疗性抗肿瘤疫苗。皮下注射两剂gDE7，与聚（I：C）混合，为先前受到表达HPV-16癌蛋白的肿瘤细胞攻击的小鼠提供了全面而持久的治疗性抗肿瘤保护。该疫苗可诱导具有细胞毒活性和效应记忆表型的多功能E7特异性CD8 + T细胞（CD44 + CD62Llow）。此外，将gDE7与聚（I：C）疫苗混合可控制肿瘤诱导的调节性T细胞和髓样来源的抑制细胞的扩增。更重要的是，gDE7在体外条件下激活了小鼠CD11c +CD8α+和人BDCA3 +树突状细胞（DC），专门针对CD8 + T细胞进行抗原交叉呈递。这些结果表明，由gD介导的特定DC群体的活化改善了抗原特异性免疫反应和抗肿瘤疫苗诱导的治疗性能。这些结果为基于gDE7的疫苗作为癌症治疗控制工具的主动免疫概念的临床测试开辟了前景。分子癌疗法；16（9）; 1922–33。©2017 AACR。