title: The antitumor efficacy of IL-24 mediated by E1A and E1B triple regulated oncolytic adenovirus.
abstract: BACKGROUND
  IL-24 (interleukin-24) is a promising, multi-functional anti-cancer agent able to selectively induce tumor cell apoptosis while sparing normal cells. Additionally, IL-24 can enhance the immune response to tumors and suppress tumor angiogenesis. In this study, we introduced IL-24 into the oncolytic adenovirus, Ad·sp·E1A((Δ24))·E1B((Δ55))·IL-24. in which E1A was engineered to target Rb (retinoblastoma) deficient or dysfunctional tumors. The survivin promoter (sp), was used to drive expression of IL-24, thereby allowing it to target most tumors. Finally, the 55 KDa gene of E1B was also deleted, thereby preventing replication in normal cells.
  
  
  RESULTS
  Ad·sp·E1A((Δ24))·E1B((Δ55))·IL-24 showed enhanced antitumor effects over the E1, singly regulated oncolytic adenovirus, ONYX-015, in in vitro experiments. Furthermore, Ad·sp·E1A((Δ24))·E1B((Δ55))·IL-24 could effectively inhibit the progression of NCI-H460 lung carcinoma xenografts in nude mice.
  
  
  METHODS
  The antitumor effect of Ad·sp·E1A((Δ24))·E1B((Δ55))·IL-24 was assessed by MTT assay and crystal violet staining in a panel of tumor cells. Cell staining and western blotting for caspase activation were used to assess apoptosis. We assessed the antitumor effects of Ad·sp·E1A((Δ24))·E1B((Δ55))·IL-24 in a xenograft model.
  
  
  CONCLUSIONS
  This is the first study to use an E1A and E1B triple regulated oncolytic adenovirus vector carrying IL-24 to treat large tumors. We attained efficient antitumor effects both in vitro and in vivo, which provides an experimental foundation for clinical cancer therapy.
authors.affiliation: Xinyuan Institute of Medicine and Biotechnology, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
authors.forename: Lian Li
authors.initials: LL
authors.lastname: Xiao
authors.forename: Yu Mei
authors.initials: YM
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Qian
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tan
authors.forename: Guo Liang
authors.initials: GL
authors.lastname: Xie
authors.forename: Kang Jian
authors.initials: KJ
authors.lastname: Zhang
authors.forename: Yi Gang
authors.initials: YG
authors.lastname: Wang
authors.forename: Xiao Yuan
authors.initials: XY
authors.lastname: Jia
authors.forename: Xin Yuan
authors.initials: XY
authors.lastname: Liu
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000378:metabolism; D017501:Adenovirus E1B Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
chemical_list: D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D007378:Interleukins; D000099180:Interleukin-24