• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Molecular Therapy >Induction of Tumor-specific Immune Response by Gene Transfer of Hsp70-cell-penetrating Peptide Fusion Protein to Tumors in Mice
【2h】

Induction of Tumor-specific Immune Response by Gene Transfer of Hsp70-cell-penetrating Peptide Fusion Protein to Tumors in Mice

机译：Hsp70细胞穿透肽融合蛋白向小鼠肿瘤的基因转移诱导肿瘤特异性免疫反应。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

To induce a tumor-specific immune response by delivering tumor-associated antigens in tumor cells to antigen-presenting cells (APCs), we designed a fusion protein which consists of heat-shock protein 70 (Hsp70) and the C-terminal 34 amino acids of herpes simplex virus VP22 protein (VP22268–301), the former having a peptide binding domain and an ability to be recognized by APCs, and the latter able to achieve cell penetration. Hsp70-VP22268–301, the fusion protein, was efficiently taken up by mouse dendritic cell (DC) line DC2.4. Major histocompatibility complex (MHC) class I–restricted presentation of an epitope peptide of ovalbumin (OVA) was examined in DC2.4, and Hsp70-VP22268–301 significantly increased the presentation of the peptide compared with Hsp70. Electroporation-assisted injection of naked plasmid vector expressing Hsp70-VP22268–301 (pHsp70-VP22268–301) into subcutaneous tumors of EG7-OVA, a mouse lymphoma–expressing OVA, significantly increased the survival of mice compared with the same treatment with pHSp70, a plasmid expressing Hsp70. Splenocytes from the pHsp70-VP22268–301-treated mice exhibited cytolytic activity against both EG7-OVA and the parent EL4, but not against mouse melanoma B16-F10, suggesting that not only OVA-derived antigens but those common to EG7-OVA and EL4 are delivered to APCs. These results provide a new therapeutic method to induce tumor-specific antitumor immunity without identifying nor isolating tumor-associated antigens.
机译：为了通过将肿瘤细胞中的肿瘤相关抗原传递给抗原呈递细胞（APC）来诱导肿瘤特异性免疫反应，我们设计了一种融合蛋白，该融合蛋白由热休克蛋白70（Hsp70）和C端34个氨基酸组成单纯疱疹病毒VP22蛋白（VP22268-301）中的一种，前者具有肽结合域并具有被APC识别的能力，而后者能够实现细胞穿透。 Hsp70-VP22268-301，融合蛋白，被小鼠树突状细胞（DC）系DC2.4有效吸收。在DC2.4中检查了主要组织相容性复合物（MHC）I类-限制的卵清蛋白（OVA）表位肽的呈递，与Hsp70相比，Hsp70-VP22268-301显着增加了该肽的呈递。用电穿孔辅助将表达Hsp70-VP22268-301（pHsp70-VP22268-301）的裸质粒载体注射到表达小鼠淋巴瘤的OVA EG7-OVA的皮下肿瘤中，与用pHSp70进行相同处理相比，小鼠的存活率显着提高，表达Hsp70的质粒。 pHsp70-VP22268–301处理过的小鼠的脾细胞对EG7-OVA和亲代EL4均表现出细胞溶解活性，但对小鼠黑素瘤B16-F10则无细胞溶解活性，这表明不仅OVA衍生抗原，而且是EG7-OVA和EL4共有的抗原交付给APC。这些结果提供了一种新的治疗方法，可以诱导肿瘤特异性抗肿瘤免疫，而无需鉴定或分离出肿瘤相关抗原。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

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