title: Treatment of patient tumor-derived colon cancer xenografts by a TRAIL gene-armed oncolytic adenovirus.
abstract: Oncolytic virus-armed gene therapy may offer new treatment options and improve the prognosis for patients with colon cancer. In this study, we sought to further confirm the antitumor activity of oncolytic virus-armed tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy in xenografts, which derived from the tumors of patients with colon cancer. To this end, we established xenotransplantable tumors from fresh surgical specimens. The histology of these xenografts maintained the features of the original tumors during passaging in nude mice. We next treated these xenografts with adenoviruses carrying TRAIL and the adenovirus E1A gene (Ad/TRAIL-E1) driven by the human telomerase reverse transcriptase promoter. The vector expressing the TRAIL gene (Ad/gTRAIL) or the E1A gene (Ad/GFP-E1) alone was used as control vector. The results demonstrated that Ad/TRAIL-E1 had more significant inhibitory effects on tumor growth than Ad/gTRAIL or Ad/GFP-E1 alone. Furthermore, we did not find any obvious treatment-related toxicity in the mice. Our results indicate that the use of an oncolytic adenoviral vector, in combination with TRAIL gene therapy, is a promising novel approach for cancer therapy.
authors.affiliation: Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhou
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.forename: X
authors.initials: X
authors.lastname: Pang
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: B
authors.initials: B
authors.lastname: Fang
authors.forename: C
authors.initials: C
authors.lastname: He
mesh_terms: D000256:Adenoviridae; D017500:Adenovirus E1A Proteins / Q000235:genetics; D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D019098:Telomerase / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D017500:Adenovirus E1A Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C509186:TERT protein, human; D019098:Telomerase