title: Gene-viro-therapy targeting liver cancer by a dual-regulated oncolytic adenoviral vector harboring IL-24 and TRAIL.
abstract: Cancer-targeting gene-viro-therapy is a promising cancer therapeutic strategy that strengthens the antitumor effect of oncolytic viruses by expressing an inserted foreign antitumor gene. To achieve liver cancer targeting and to improve the safety of the ZD55 vector (a widely-used E1B55KD gene-deleted oncolytic adenoviral vector (OV), we previously constructed), we designed a novel OV named Ad·AFP·D55 that selectively replicates in hepatocellular carcinoma (HCC) cells by replacing the E1A promoter with the liver-cancer specific α-Fetoprotein (AFP) promoter based on the ZD55 vector. We found that the oncolytic adenoviruses Ad·AFP·D55-IL-24 and Ad·AFP·D55-TRAIL express tumor-suppressor gene interleukin-24 (IL-24) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), respectively, significantly suppressed the HCC cell growth in vitro by inducing apoptosis by the caspase-8 and mitochondria-dependent caspase-9 signaling pathways. Furthermore, the combined treatment of Ad·AFP·D55-IL-24 and Ad·AFP·D55-TRAIL showed strong antitumor effects in vivo by significantly inhibiting the tumor growth in HCC HuH-7 cell xenograft mice, and markedly increasing animal survival rate. Therefore, this novel HCC cell-targeting OV carrying tumor-suppressor genes may provide a promising approach for liver cancer gene therapy.
authors: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, China.
authors: X
authors: X
authors: Liu
authors: X
authors: X
authors: Cao
authors: R
authors: R
authors: Wei
authors: Y
authors: Y
authors: Cai
authors: H
authors: H
authors: Li
authors: J
authors: J
authors: Gui
authors: D
authors: D
authors: Zhong
authors: X-Y
authors: XY
authors: Liu
authors: K
authors: K
authors: Huang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
chemical_list: D007378:Interleukins; D053221:TNF-Related Apoptosis-Inducing Ligand; D000099180:Interleukin-24