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