Potent antitumor activity of oncolytic adenovirus expressing mda-7/IL-24 for colorectal cancer.
It has been demonstrated that interleukin 24 (IL-24, also called melanoma differentiation associated gene 7) exerts antitumor activity. In this study, we investigated whether oncolytic adenovirus-mediated gene transfer of IL-24 could induce strong antitumor activity. A tumor-selective replicating adenovirus expressing IL-24 (ZD55-IL-24) was constructed by insertion of an IL-24 expression cassette into the ZD55 vector, which is based on deletion of the adenoviral E1B 55-kDa gene. ZD55-IL-24 could express substantially more IL-24 than Ad-IL-24 because of replication of the vector. It has been shown that ZD55-IL-24 exerted a strong cytopathic effect and significant apoptosis in tumor cells with p53 dysfunction. Moreover, no cytotoxic and apoptotic effects could be seen in normal cells infected with ZD55-IL-24. Expression of IL-24 did not interfere with viral replication induced by oncolytic adenovirus. Activation of caspase 3 and caspase 9, and induction of bax gene expression, were involved in tumor cell apoptosis induced by ZD55-IL-24. Treatment of established tumors with ZD55-IL-24 showed much stronger antitumor activity than that induced by ONYX-015 or Ad-IL- 24. These data indicated that oncolytic adenovirus expressing IL-24 could exert potential antitumor activity and offer a novel approach to cancer therapy.
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Lili
L
Zhao
Jinfa
J
Gu
Aiwen
A
Dong
Yanhong
Y
Zhang
Liu
L
Zhong
Lingfeng
L
He
Yigang
Y
Wang
Jinhe
J
Zhang
Zilai
Z
Zhang
Jin
J
Huiwang
Qijun
Q
Qian
Cheng
C
Qian
Xinyuan
X
Liu
D000256:Adenoviridae / Q000235:genetics*; D017501:Adenovirus E1B Proteins / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
D017501:Adenovirus E1B Proteins; D020169:Caspases; D007378:Interleukins; D000099180:Interleukin-24