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Human Gene Therapy
DNA Vaccines Employing Intracellular Targeting Strategies and a Strategy to Prolong Dendritic Cell Life Generate a Higher Number of CD8+ Memory T Cells and Better Long-Term Antitumor Effects Compared with a DNA Prime–Vaccinia Boost Regimen
To cite this article:
Tae Woo Kim, Jin-Hyup Lee, Liangmei He, David A. K. Boyd, Chien-Fu Hung, T.-C. Wu.
Human Gene Therapy.
January 2005,
16(1): 26-34.
doi:10.1089/hum.2005.16.26.
Tae Woo Kim Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205. Department of Advanced Materials, Korea Research Institute of Chemical Technology, Daejeon 305-600, Korea. Jin-Hyup Lee Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205. Liangmei He Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205. David A. K. Boyd Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205. Chien-Fu Hung Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205. Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21205. Dr. T.-C. Wu Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205. Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21205. Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD 21205. Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD 21205. We have previously shown that intradermal coadministration of DNA encoding Bcl-xL, an antiapoptotic protein, with DNA encoding E7 antigen linked to the sorting signal of the lysosome-associated membrane protein type 1 (Sig/E7/LAMP-1) prolongs dendritic cell life and enhances antigen presentation through the MHC class I and II pathways. In the current study, we compared this approach with a conventional DNA prime–vaccinia boost protocol on the basis of their ability to generate antigen-specific CD8+ memory T cells and longterm antitumor effects against an E7-expressing tumor. Mice primed and boosted with Sig/E7/LAMP-1 DNA mixed with Bcl-xL DNA generated significantly higher numbers of E7-specific CD8+ memory T cells and a better long-term protective antitumor effect compared with mice primed with Sig/E7/LAMP-1 DNA and boosted with Sig/E7/LAMP-1 vaccinia (Vac-Sig/E7/LAMP-1). Furthermore, coadministration of Sig/E7 /LAMP-1 DNA mixed with Bcl-xL DNA also generated higher avidity E7-specific CD8+ T cells than did vaccination with Sig/E7/LAMP-1 DNA followed by a Vac-Sig/E7/LAMP-1 booster. Our results indicate that coadministration of a DNA vaccine employing intracellular targeting strategies and a DNA encoding antiapoptotic proteins may potentially generate a higher number of memory CD8+ T cells and better long-term protective antitumor effects compared with the conventional DNA prime–vaccinia boost regimen.  This paper was cited by:Equivalent stimulation of naive and memory CD8 T cells by DNA vaccination: a dendritic cell-dependent process Sammy Bedoui, Gayle M Davey, Andrew M Lew, William R Heath Immunology and Cell Biology. Feb 2009 CrossRef Immunotherapy for head and neck cancer Annie A. Wu, Kevin J. Niparko, Sara I. Pai Journal of Biomedical Science. Jun 2008, Vol. 15, No. 3: 275-289 CrossRef Antigen-specific immunotherapy of cervical and ovarian cancer Chien-Fu Hung, T. C. Wu, Archana Monie, Richard Roden Immunological Reviews. May 2008, Vol. 222, No. 1: 43-69 CrossRef Adjuvant properties of listeriolysin O protein in a DNA vaccination strategy Xiaohui Peng, John Treml, Yvonne Paterson Cancer Immunology, Immunotherapy. Apr 2007, Vol. 56, No. 6: 797-806 CrossRef DNA vaccines for HIV/AIDS Jeffrey B Ulmer, Britta Wahren, Margaret A Liu Current Opinion in HIV and AIDS. Aug 2006, Vol. 1, No. 4: 309-313 CrossRef ‘Survival gene’ Bcl-xl potentiates DNA-raised antitumor immunity J H Kim, J Chen, N Majumder, H Lin, L D Falo, Z You Gene Therapy. Nov 2005, Vol. 12, No. 20: 1517-1525 CrossRef |
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