Potent antitumor efficacy of interleukin-18 delivered by conditionally replicative adenovirus vector in renal cell carcinoma-bearing nude mice via inhibition of angiogenesis.
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.
Zheng
Jun-Nian
JN
Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China. jnzheng@xzmc.edu.cn
Pei
Dong-Sheng
DS
Sun
Fang-Hao
FH
Liu
Xin-Yuan
XY
Mao
Li-Jun
LJ
Zhang
Bao-Fu
BF
Wen
Ru-Min
RM
Xu
Wei
W
Shi
Zhen
Z
Liu
Jun-Jie
JJ
Li
Wang
W
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
D020382:Interleukin-18