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Complete eradication of hepatomas using an oncolytic adenovirus containing AFP promoter controlling E1A and an E1B deletion to drive IL-24 expression

Cancer Gene Therapy volume 19, pages 619–629 (2012)Cite this article

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Abstract

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.

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Acknowledgements

We thank YanLing Ren and LanYing Sun for kind help in cell culture, and we also thank Prof YouChen Xu for good comments for writing. This work was supported by the National Nature Science Foundation of China (No. 30623003), the National Basic Research Program of China (973 Program) (No. 2010CB529901), Important National Science and Technology Specific Project of Hepatitis and Hepatoma Related Program (2008ZX10002-023), the National Basic Research Committee of Science and Technology (Nos. 06ZR14072 and 074119508); and the ZheJiang Sci-Tech University Grant No.1016819-Y.

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  1. K-J Zhang and J Zhang: These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, Shanghai, China

    K-J Zhang, L-C Yan, X Cao, N Wei, X-R Liu & X-Y Liu

  2. XinYuan Institute of Medicine and Biotechnology, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang Province, China

    J Zhang, Y-M Wu, J Qian, X-J Liu, X-M Zhou, R-J Xiao, Y-G Wang, B Tang, X-Y Jiao, K Chen & X-Y Liu

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Zhang, KJ., Zhang, J., Wu, YM. et al. Complete eradication of hepatomas using an oncolytic adenovirus containing AFP promoter controlling E1A and an E1B deletion to drive IL-24 expression. Cancer Gene Ther 19, 619–629 (2012). https://doi.org/10.1038/cgt.2012.40

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