title: Combination of E2F-1 promoter-regulated oncolytic adenovirus and cytokine-induced killer cells enhances the antitumor effects in an orthotopic rectal cancer model.
abstract: 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.
authors.affiliation: Institute of General Surgery, Chinese PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yan
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Xu
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Peiming
authors.initials: P
authors.lastname: Sun
authors.forename: Hailiang
authors.initials: H
authors.lastname: Liu
authors.forename: Qinghao
authors.initials: Q
authors.lastname: Fan
authors.forename: Kai
authors.initials: K
authors.lastname: Liang
authors.forename: Wentao
authors.initials: W
authors.lastname: Liang
authors.forename: Huiwei
authors.initials: H
authors.lastname: Sun
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Du
authors.forename: Rong
authors.initials: R
authors.lastname: Li
mesh_terms: D000256:Adenoviridae; D003131:Combined Modality Therapy; D055612:Cytokine-Induced Killer Cells / Q000276:immunology; D050687:E2F1 Transcription Factor / Q000096:biosynthesis* / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000276:immunology; D011401:Promoter Regions, Genetic; D012004:Rectal Neoplasms / Q000276:immunology* / Q000628:therapy* / Q000821:virology
chemical_list: D050687:E2F1 Transcription Factor
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