• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Human gene therapy. Clinical development >Enhanced Therapeutic Effects Conferred by an Experimental DNA Vaccine Targeting Human Papillomavirus-lnduced Tumors
【24h】

Enhanced Therapeutic Effects Conferred by an Experimental DNA Vaccine Targeting Human Papillomavirus-lnduced Tumors

机译：针对人乳头瘤病毒诱导的肿瘤的实验性DNA疫苗赋予的增强的治疗效果

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Human papillomavirus (HPV) infection is responsible for all cervical cancer cases, other anogenital cancers, and head and neck tumors. The epidemiological relevance of HPV-induced tumors reinforces the need for the development of therapeutic antitumor vaccines. Clinical trials with different vaccine formulations, particularly DNA vaccines, have provided promising results but have still been unable to achieve the immunogenicity required for use in infected patients. In experimental conditions, anticancer HPV-specific vaccines induced E7-specific CD8~+ T-cell responses but did not confer full therapeutic antitumor protection in mice with transplanted HPV-expressing TC-1 cells, which are the most frequently used nonclinical protection correlate for antitumor effects. Our group has developed a DNA vaccine strategy based on the fusion of HPV oncoproteins to the herpes virus gD protein. This vaccine promoted the induction of antigen-specific cytotoxic CD8~+ T-cell responses and partial antitumor therapeutic effects based on the blockade of coinhibitory signals and the enhancement of coactivation mechanisms. In the present study, we report conditions leading to full therapeutic antitumor effects using the TC-1 cell murine model after a single vaccine dose. The combination of a coadministered plasmid encoding IL-2, optimization of the coding sequence for mammalian cells, and the use of different delivery routes resulted in enhancements of the E7-specific cytotoxic CD8~+ T-cell responses and full therapeutic protection under experimental conditions. The combination of these strategies augmented the potency of the DNA vaccine formulation to levels not previously achieved by other therapeutic antitumor vaccines under similar experimental conditions, including some that have been taken to clinical trials.
机译：人乳头瘤病毒（HPV）感染负责所有子宫颈癌，其他肛门生殖器癌以及头颈部肿瘤。 HPV诱导的肿瘤的流行病学相关性增强了开发治疗性抗肿瘤疫苗的需要。使用不同疫苗制剂（尤其是DNA疫苗）的临床试验已提供了令人鼓舞的结果，但仍无法获得用于感染患者所需的免疫原性。在实验条件下，抗癌HPV特异性疫苗可诱导E7特异性CD8〜+ T细胞应答，但不能在表达HPV的TC-1细胞移植的小鼠中提供完全的治疗性抗肿瘤保护，这是最常用的非临床保护作用抗肿瘤作用。我们小组基于HPV癌蛋白与疱疹病毒gD蛋白的融合，开发了一种DNA疫苗策略。该疫苗基于共抑制信号的阻断和共激活机制的增强，促进了抗原特异性细胞毒性CD8〜+ T细胞应答的诱导和部分抗肿瘤治疗作用。在本研究中，我们报告了在单剂疫苗后使用TC-1细胞鼠模型可导致完全治疗性抗肿瘤作用的情况。共同编码IL-2的质粒，优化哺乳动物细胞的编码序列以及使用不同的递送途径相结合，可增强E7特异性细胞毒性CD8〜+ T细胞反应，并在实验条件下提供全面的治疗保护。这些策略的组合将DNA疫苗制剂的效价提高到了在类似的实验条件下，包括其他已用于临床试验的其他抗肿瘤治疗疫苗以前无法达到的水平。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号