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

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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 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.