Complete eradication of hepatomas using an oncolytic adenovirus containing AFP promoter controlling E1A and an E1B deletion to drive IL-24 expression.
Interleukin (IL)-24, a promising therapeutic gene, has been widely used for Cancer Targeting Gene-Viro-Therapy (CTGVT). In this study, IL-24 was inserted into an oncolytic adenovirus in which the E1A gene is driven by an enhanced, short α-fetoprotein (AFP) promoter and the E1B gene is completely deleted to form Ad.enAFP-E1A-ΔE1B-IL-24. This construct has a potent antitumor effect on liver cancer cell lines in vitro, but little or no effect on normal cell lines, such as L-02 and QSG-7701. In vivo, the complete elimination of Huh-7 liver cancer in nude mice with Ad.enAFP-E1A-ΔE1B-IL-24 intratumor injection was observed. The design of Ad.enAFP-E1A-ΔE1B-IL-24 and its potent antitumor effect on liver cancer have not been published previously. The mechanism of the potent antitumor effect of Ad.enAFP-E1A-ΔE1B-IL-24 is due to the upregulation of GADD34 and intrinsic and extrinsic apoptotic signaling.
State Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, China.
K-J
KJ
Zhang
J
J
Zhang
Y-M
YM
Wu
J
J
Qian
X-J
XJ
Liu
L-C
LC
Yan
X-M
XM
Zhou
R-J
RJ
Xiao
Y-G
YG
Wang
X
X
Cao
N
N
Wei
X-R
XR
Liu
B
B
Tang
X-Y
XY
Jiao
K
K
Chen
X-Y
XY
Liu
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D017500:Adenovirus E1A Proteins / Q000235:genetics*; D017501:Adenovirus E1B Proteins / Q000235:genetics*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D002470:Cell Survival; D005260:Female; D017353:Gene Deletion; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D023041:Xenograft Model Antitumor Assays; D000509:alpha-Fetoproteins / Q000235:genetics*; D000099180:Interleukin-24
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D007378:Interleukins; D000509:alpha-Fetoproteins; D000099180:Interleukin-24; C097353:AFP protein, human