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An HDAC inhibitor enhances the antitumor activity of a CMV promoter-driven DNA vaccine

Cancer Gene Therapy volume 17, pages 203–211 (2010)Cite this article

Abstract

The cytomegalovirus (CMV) promoter is considered to be one of the strongest promoters for driving the in vivo expression of genes encoded by DNA vaccines. However, the efficacy of DNA vaccines has so far been disappointing (particularly in humans), and this might be explained in part by histone deacetylase (HDAC)-mediated chromatin condensation. Hence, we sought to investigate whether increasing the expression of DNA vaccine antigens with the HDAC inhibitor OSU-HDAC42 would enhance the efficacy of DNA vaccines in vivo. A luciferase assay was used to determine the effects of OSU-HDAC42 on CMV promoter-driven DNA plasmids in vitro and in vivo. Three HDAC inhibitors were able to activate expression from the CMV promoter in NIH3T3 cells and MBT-2 bladder cancer cells. The expression of luciferase was significantly enhanced by co-administration of pCMV-luciferase and OSU-HDAC42 in mice. To explore whether OSU-HDAC42 could enhance the specific antitumor activity of a neu DNA vaccine driven by the CMV promoter, we evaluated therapeutic effects and immune responses in a mouse tumor natively overexpressing HER2/neu. Mice receiving OSU-HDAC42 in combination with the CMV-promoter neu DNA vaccine exhibited stronger antitumor effects than mice given the DNA vaccine only. In addition, a correlation between the antitumor effects and the specific cellular immune responses was observed in the mice receiving the DNA vaccine and OSU-HDAC42.

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Acknowledgements

This study was supported by Grants from the Taichung Veterans General Hospital and National Chung Hsing University (TCVGH-NCHU-987614) Taichung, Taiwan, and in part by the Ministry of Education, Taiwan, ROC under the ATU plan.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Taiwan, ROC

    M-D Lai & C-F Tu

  2. Institute of Basic Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Taiwan, ROC

    M-D Lai & M-C Yen

  3. Center for Gene Regulation and Signal Transduction Research, National Cheng Kung University, Tainan, Taiwan, Taiwan, ROC

    M-D Lai

  4. Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, USA

    C-S Chen

  5. Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, Taiwan, ROC

    C-R Yang & S-Y Yuan

  6. Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan, Taiwan, ROC

    J-J Tsai

  7. Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, Taiwan, ROC

    J-J Tsai & C-C Lin

  8. Institute of Medical Technology, College of Life Science, National Chung Hsing University, Taichung, Taiwan, Taiwan, ROC

    C-C Wang & C-C Lin

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  1. M-D Lai
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Correspondence to C-C Lin.

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Lai, MD., Chen, CS., Yang, CR. et al. An HDAC inhibitor enhances the antitumor activity of a CMV promoter-driven DNA vaccine. Cancer Gene Ther 17, 203–211 (2010). https://doi.org/10.1038/cgt.2009.65

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