Oncolytic adenovirus expressing interleukin-18 induces significant antitumor effects against melanoma in mice through inhibition of angiogenesis.
It has been shown 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. It has been shown that ZD55-IL-18 exerted a strong cytopathic effect and significant apoptosis in tumor cells. ZD55-IL-18 significantly decreased vascular endothelial growth factor and CD34 expression in the melanoma cells. Treatment of established tumors with ZD55-IL-18 showed much stronger antitumor activity than that induced by ZD55-EGFP (enhanced green fluorescent protein) or Ad-IL-18. These data indicated that oncolytic adenovirus expressing IL-18 could exert potential antitumor activity through inhibition of angiogenesis and offer a novel approach to melanoma therapy.
Zheng
J-N
JN
Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China. jnzheng@xzmc.edu.cn
Pei
D-S
DS
Mao
L-J
LJ
Liu
X-Y
XY
Sun
F-H
FH
Zhang
B-F
BF
Liu
Y-Q
YQ
Liu
J-J
JJ
Li
W
W
Han
D
D
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000628:therapy* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000628:therapy / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D020382:Interleukin-18