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

Tae Woo Kim, Jin Hyup Lee, Liangmei He, David A K Boyd, Chien Fu Hung, T. C. Wu

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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 long-term 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.

Original languageEnglish
Pages (from-to)26-34
Number of pages9
JournalHuman Gene Therapy
Volume16
Issue number1
DOIs
Publication statusPublished - 2005 Jan 1
Externally publishedYes

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Vaccinia
DNA Vaccines
Dendritic Cells
T-Lymphocytes
DNA
Lysosome-Associated Membrane Glycoproteins
CD8 Antigens
Antigen Presentation
Vaccination
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

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abstract = "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 long-term 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.",
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AU - Lee, Jin Hyup

AU - He, Liangmei

AU - Boyd, David A K

AU - Hung, Chien Fu

AU - Wu, T. C.

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