title: Enhanced antitumor effect of combining TRAIL and MnSOD mediated by CEA-controlled oncolytic adenovirus in lung cancer.
abstract: Lung cancer, especially adenocarcinoma, is one of the leading causes of death in the world. Carcinoembryonic antigen (CEA), a superb non-small-cell lung cancer marker candidate, showed a beneficial effect in cancer therapy with oncolytic adenovirus in recent studies. Cancer-targeting dual gene-virotherapy delivers two therapeutic genes, linked by a connexon, in the replication-deficient vector instead of one gene so that they can work in common. In this study, we constructed a tumor-specific oncolytic adenovirus, CD55-TRAIL-IETD-MnSOD. The virus has the fusion protein complementary DNAs for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and for manganese superoxide dismutase (MnSOD) complementary DNA linked through a 4-amino acid caspase-8 cleavage site (IETD), and uses a CEA promoter to control virus E1A express. This is the first work to use a CEA promoter-regulated oncolytic adenovirus carrying two therapeutic genes for cancer research. Its targeting and anticancer capacity was evaluated by in vitro and in vivo experiments. The results indicated that CD55-TRAIL-IETD-MnSOD caused more cell apoptosis than CD55-TRAIL or CD55-MnSOD alone, or their combination in vitro, with low cytotoxicity of normal cells. In the A549 tumor xenograft model in nude mice, data showed that CD55-TRAIL-IETD-MnSOD could effectively suppress tumor growth than single gene groups, with no histological damage in liver, spleen or kidney tissues. Thus, the CEA-regulated dual-gene oncolytic virus CD55-TRAIL-IETD-MnSOD may be a novel potential therapy for lung cancer.
authors.affiliation: Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China.
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China.|Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Ma
authors.affiliation: Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China.
authors.forename: B
authors.initials: B
authors.lastname: Xiao
authors.affiliation: School of Public health, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: F
authors.initials: F
authors.lastname: Huang
authors.affiliation: Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China.
authors.forename: P
authors.initials: P
authors.lastname: Huang
authors.affiliation: Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Ying
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.affiliation: Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D023061:Gene Order; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D002272:Carcinoembryonic Antigen; D053221:TNF-Related Apoptosis-Inducing Ligand; D013482:Superoxide Dismutase