title: Potent antitumor efficacy of interleukin-18 delivered by conditionally replicative adenovirus vector in renal cell carcinoma-bearing nude mice via inhibition of angiogenesis.
abstract: It has been demonstrated that interleukin 18 (IL-18) exerts antitumor activity. In this study, we investigated whether oncolytic adenovirus-mediated gene transfer of IL-18 could induce strong antitumor activity. A tumor-selective replicating adenovirus expressing IL-18 (ZD55-IL-18) was constructed by insertion of an IL-18 expression cassette into the ZD55 vector, which is based on deletion of the adenoviral E1B 55-kDa gene. ZD55-IL-18 could express substantially more IL-18 than Ad-IL-18 because of replication of the vector. It has been shown that ZD55-IL-18 exerted a strong cytopathic effect and significant apoptosis in renal cell carcinoma. ZD55-IL-18 significantly decreased VEGF and CD34 expression in the tumor cells. Treatment of established tumors with ZD55-IL-18 showed much stronger antitumor activity than that induced by ZD55-EGFP or Ad-IL-18. These data indicated that oncolytic adenovirus expressing IL-18 could exert potential antitumor activity via inhibition of angiogenesis and offer a novel approach to cancer therapy.
authors.affiliation: Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China. jnzheng@xzmc.edu.cn
authors.forename: Jun-Nian
authors.initials: JN
authors.lastname: Zheng
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Pei
authors.forename: Fang-Hao
authors.initials: FH
authors.lastname: Sun
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Liu
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Mao
authors.forename: Bao-Fu
authors.initials: BF
authors.lastname: Zhang
authors.forename: Ru-Min
authors.initials: RM
authors.lastname: Wen
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shi
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Liu
authors.forename: Wang
authors.initials: W
authors.lastname: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000502:physiology; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000235:genetics / Q000628:therapy* / Q000821:virology; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D020287:In Situ Nick-End Labeling; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics*; D007680:Kidney Neoplasms / Q000098:blood supply / Q000235:genetics / Q000628:therapy* / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy; D050130:Oncolytic Virotherapy; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D020382:Interleukin-18