Combination of E2F-1 promoter-regulated oncolytic adenovirus and cytokine-induced killer cells enhances the antitumor effects in an orthotopic rectal cancer model

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• 作者：Yang Yan (1)
  Yingxin Xu (1)
  Yunshan Zhao (1)
  Li Li (1)
  Peiming Sun (1)
  Hailiang Liu (1)
  Qinghao Fan (1)
  Kai Liang (1)
  Wentao Liang (1)
  Huiwei Sun (1)
  Xiaohui Du (1) (2)
  Rong Li (1) (2)
  
• 关键词：E2F ; 1 ; CIK cell ; Orthotopic rectal cancer
• 刊名：Tumor Biology
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：35
• 期：2
• 页码：1113-1122
• 全文大小：744 KB
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• 作者单位：Yang Yan (1)
  Yingxin Xu (1)
  Yunshan Zhao (1)
  Li Li (1)
  Peiming Sun (1)
  Hailiang Liu (1)
  Qinghao Fan (1)
  Kai Liang (1)
  Wentao Liang (1)
  Huiwei Sun (1)
  Xiaohui Du (1) (2)
  Rong Li (1) (2)
  
  1. Institute of General Surgery, Chinese PLA General Hospital, Beijing, People鈥檚 Republic of China
  2. General Surgery Department, Chinese PLA General Hospital, 28 Fuxing Road, Haidian, Beijing, 100853, People鈥檚 Republic of China
  
• ISSN：1423-0380

文摘

Due to the anatomical structure of the rectum, the treatment of rectal cancer remains challenging. Ad-E2F, an oncolytic adenovirus containing the E2F-1 promoter, can selectively replicate within and kill cancer cells derived from solid tumors. Thus, this virus provides a novel approach for the treatment of rectal cancer. Given the poor efficacy and possible adverse reactions that arise from the use of oncolytic virus alone and the results of our analysis of the efficacy of Ad-E2F in the treatment of rectal cancer, we investigated the use of oncolytic adenovirus in combination with adoptive immunotherapy using cytokine-induced killer (CIK) cells as a therapeutic treatment for rectal cancer. Our results illustrated that E2F-1 gene expression is higher in rectal cancer tissue than in normal tissue. Furthermore, the designed oncolytic adenovirus Ad-E2F is capable of selectively killing colorectal cell lines but has no significant effect on CIK cells. The results of in vitro and in vivo experiments demonstrated that combined therapy with Ad-E2F and CIK cells produce stronger antitumor effects than the administration of Ad-E2F or CIK cells alone. For low rectal cancers that are suitable for intratumoral injection, local injections of oncolytic viruses in combination with CIK cell-based adoptive immunotherapy may be suitable as a novel comprehensive therapeutic approach.