DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor

He Zhou, Yunping Luo, Jeng Fan Lo, Charles D. Kaplan, Masato Mizutani, Noriko Mizutani, Jiing Dwan Lee, F. James Primus, Jürgen C. Becker, Rong Xiang, Ralph A. Reisfeld*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

The interaction of NKG2D, a stimulatory receptor expressed on natural killer (NK) cells and activated CD8+ T cells, and its ligands mediates stimulatory and costimulatory signals to these cells. Here, we demonstrate that DNA-based vaccines, encoding syngeneic or allogeneic NKG2D ligands together with tumor antigens such as survivin or carcinoembryonic antigen, markedly activate both innate and adaptive antitumor immunity. Such vaccines result in highly effective, NK- and CD8+ T cell-mediated protection against either breast or colon carcinoma cells in prophylactic and therapeutic settings. Notably, this protection was irrespective of the NKG2D ligand expression level of the tumor cells. Hence, this strategy has the potential to lead to widely applicable and possibly clinically useful DNA-based cancer vaccines.

Original languageEnglish
Pages (from-to)10846-10851
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number31
DOIs
StatePublished - 2 Aug 2005

Keywords

  • NK cells
  • NKG2D ligands
  • Peyer's patches
  • Survivin
  • T cells

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