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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.

Kim TW, Lee JH, He L, Boyd DA, Hung CF, Wu TC

Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.

We have previously shown that intradermal coadministration of DNA encoding Bcl-x(L), 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-x(L) 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-x(L) 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.

Published 10 February 2005 in Hum Gene Ther, 16(1): 26-34.
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