Journal
CANCER GENE THERAPY
Volume 19, Issue 9, Pages 619-629Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2012.40
Keywords
Cancer Targeting Gene-Viro-Therapy; complete eradication; E1B deletion; hepatoma specificity; IL-24
Categories
Funding
- National Nature Science Foundation of China [30623003]
- National Basic Research Program of China (973 Program) [2010CB529901]
- Important National Science and Technology Specific Project of Hepatitis and Hepatoma Related Program [2008ZX10002-023]
- National Basic Research Committee of Science and Technology [06ZR14072, 074119508]
- ZheJiang Sci-Tech University [1016819-Y]
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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 alpha-fetoprotein (AFP) promoter and the E1B gene is completely deleted to form Ad.enAFP-E1A-Delta E1B-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-Delta E1B-IL-24 intratumor injection was observed. The design of Ad.enAFP-E1A-Delta E1B-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-Delta E1B-IL-24 is due to the upregulation of GADD34 and intrinsic and extrinsic apoptotic signaling.
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