DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor |
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Authors: | Zhou He Luo Yunping Lo Jeng-fan Kaplan Charles D Mizutani Masato Mizutani Noriko Lee Jiing-Dwan Primus F James Becker Jürgen C Xiang Rong Reisfeld Ralph A |
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Affiliation: | Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. |
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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. |
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