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Antitumor effects of oncolytic adenovirus armed with PSA-IZ-CD40L fusion gene against prostate cancer

Gene Therapy volume 21, pages 723–731 (2014)Cite this article

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Abstract

Advanced prostate cancer (PC) still remains incurable. Novel immunogene therapy shows promise as treatment strategy that can target both localized and metastasized PC. In this study, we have developed a PC-specific oncolytic adenovirus (Ad-PL-PPT-E1A) armed with fusion gene of prostate-specific antigen and CD40 ligand, and aimed to evaluate its therapeutic effect in vitro and in vivo. After they were rescued in human embryonic kidney 293 cells, we confirmed that Ad-PL-PPT-E1A could mediate the expression of E1A efficiently and produce abundant progeny viruses in PC cells in vitro. Our data showed that Ad-PL-PPT-E1A induced apoptosis and resulted in specific oncolytic toxicity in PC cells, which was detected by Annexin-V staining and crystal violet, respectively. After stimulation with lysates, immune phenotypes and cytokines expression of human dendritic cells was detected by flow cytometry and real-time polymerase chain reaction, respectively. And, the results showed that the lysate of Ad-PL-PPT-E1A-infected LNCaP cells upregulated the expression of CD80, CD83, CD86 and mRNA level of interleukin-6 (IL-6), IL-12, IL-23 and tumor necrosis factor-α significantly. In established PC3M cell-xenografted mouse models, Ad-PL-PPT-E1A treatment improved the survival and suppressed the tumor growth obviously. In conclusion, Ad-PL-PPT-E1A exhibited enhanced antitumor activity is a promising approach for gene therapy of advanced PC.

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Acknowledgements

This work was supported by grants from the National High Technology Research and Development Program of China (863 Program) (Nos. 2012AA020807 and 2014AA020515), the National Basic Research and Development of China (973 Program) (No. 2012CB518205) and the National Natural Science Foundation of China (No. 30901379).

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  1. Y-F Yang and S-Y Xue: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China

    Y-F Yang, S-Y Xue, F-J Xiao, Q-W Zhang, C-T Wu, H Wang & L-S Wang

  2. Chinese Center for Disease Control and Prevention, Institute for Viral Disease Control and Prevention, Beijing, People's Republic of China

    Z-Z Lu

  3. Department of Hematology, Peking University First Hospital, Beijing, People's Republic of China

    Y Yin

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  1. Y-F Yang
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Correspondence to H Wang or L-S Wang.

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Yang, YF., Xue, SY., Lu, ZZ. et al. Antitumor effects of oncolytic adenovirus armed with PSA-IZ-CD40L fusion gene against prostate cancer. Gene Ther 21, 723–731 (2014). https://doi.org/10.1038/gt.2014.46

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