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Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism

Gene Therapy volume 15, pages 1007–1016 (2008)Cite this article

Abstract

A novel method for generating an antigen-specific cancer vaccine and immunotherapy has emerged using a DNA vaccine. However, antigen-presenting cells (APCs) have a limited life span, which hinders their long-term ability to prime antigen-specific T cells. Connective tissue growth factor (CTGF) has a role in cell survival. This study explored the intradermal administration of DNA encoding CTGF with a model tumor antigen, human papilloma virus type 16 E7. Mice vaccinated with CTGF/E7 DNA exhibited a dramatic increase in E7-specific CD4+ and CD8+ T-cell precursors. They also showed an impressive antitumor effect against E7-expressing tumors compared with mice vaccinated with the wild-type E7 DNA. The delivery of DNA encoding CTGF and E7 or CTGF alone could prolong the survival of transduced dendritic cells (DCs) in vivo. In addition, CTGF/E7-transduced DCs could enhance a higher number of E7-specific CD8+ T cells than E7-transduced DCs. By prolonging the survival of APCs, DNA vaccine encoding CTGF linked to a tumor antigen represents an innovative approach to enhance DNA vaccine potency and holds promise for cancer prophylaxis and immunotherapy.

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Acknowledgements

This study was support by grants from the National Science Committee of Taiwan (NSC95-2314-B002-285). We would like to thank Dr TC Wu (Johns Hopkins Medical Institutes, Baltimore, MD, USA) for plasmid pcDNA3-E7/GFP and TC-1 tumor cells.

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Authors and Affiliations

  1. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

    W-F Cheng & Y-N Su

  2. Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan

    W-F Cheng, M-C Chang, C-N Lee, H-W Lin, C-Y Hsieh & C-A Chen

  3. Department of Anesthesiology, College of Medicine, National Taiwan University, Taipei, Taiwan

    W-Z Sun

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Correspondence to C-A Chen.

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Cheng, WF., Chang, MC., Sun, WZ. et al. Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism. Gene Ther 15, 1007–1016 (2008). https://doi.org/10.1038/gt.2008.25

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