title: Potent growth-inhibitory effect of TRAIL therapy mediated by double-regulated oncolytic adenovirus on osteosarcoma.
abstract: Osteosarcoma (OS) severely threatens the health of young people and understanding on the molecular mechanisms of OS etiology enables gene therapy to become an effective therapeutic modality. However, insufficient expression level of genes using existing vectors limits the clinical application of gene therapy for OS. To solve the problem, we developed an oncolytic adenoviral vector, OAT, which can selectively and efficiently replicate in OS cells to enhance the expression of transferred genes. We demonstrated that OAT-mediated TRAIL expression is significantly elevated after infection of OS cells than replication-incompetent Ad5 vector. Increased antitumor capacity was observed in OS cells after OAT-TRAIL treatment both in vitro and in vivo. In normal cells, adenoviral replication, TRAIL expression and growth-inhibiting effect were quite limited when OAT-TRAIL was administrated, showing a high biosafety of this oncolytic adenoviral vector. Collectively, we generated an efficient and promising expression vector for OS gene therapy.
authors.affiliation: Department of Orthopaedic Surgery, General Hospital of People's Liberation Army, Beijing 100853, China.
authors.forename: Chunbao
authors.initials: C
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Chunbao
authors.forename: Qianpeng
authors.initials: Q
authors.lastname: Cheng
authors.forename: Cheng
authors.initials: C
authors.lastname: Qianpeng
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Liu
authors.initials: L
authors.lastname: Jia
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Wang
authors.initials: W
authors.lastname: Bin
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Chen
authors.forename: Chen
authors.initials: C
authors.lastname: Dongfeng
authors.forename: Yujie
authors.initials: Y
authors.lastname: Liu
authors.forename: Liu
authors.initials: L
authors.lastname: Yujie
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000628:therapy*; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000166:cytology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000628:therapy*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins