Original Article

Gene Therapy (2008) 15, 1007–1016; doi:10.1038/gt.2008.25; published online 20 March 2008

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

W-F Cheng1,2, M-C Chang2, W-Z Sun3, C-N Lee2, H-W Lin2, Y-N Su1, C-Y Hsieh2 and C-A Chen2

  1. 1Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
  2. 2Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan
  3. 3Department of Anesthesiology, College of Medicine, National Taiwan University, Taipei, Taiwan

Correspondence: Professor C-A Chen, Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, 7 Chung-Shan South Road, Taipei 100, Taiwan. E-mail: chianchen@ntu.edu.tw

Received 13 April 2007; Revised 8 January 2008; Accepted 8 January 2008; Published online 20 March 2008.

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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.

Keywords:

connective tissue growth factor, DNA vaccine, immunotherapy, HPV16, E7 antigen

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