DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor.
DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor.
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DOI：
10.1073/pnas.0502208102
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发表时间：
2005-08
影响因子：
11.1
通讯作者：
He Zhou;Yunping Luo;Jeng-Fan Lo;C. Kaplan;M. Mizutani;N. Mizutani;Jiing-Dwan Lee;F. Primus;J. Becker;R. Xiang;R. Reisfeld
中科院分区：
文献类型：
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作者：
He Zhou;Yunping Luo;Jeng-Fan Lo;C. Kaplan;M. Mizutani;N. Mizutani;Jiing-Dwan Lee;F. Primus;J. Becker;R. Xiang;R. Reisfeld
NKG 2D是一种在自然杀伤（NK）细胞和活化的CD 8（+）T细胞上表达的刺激性受体，其与配体的相互作用介导了对这些细胞的刺激和共刺激信号。在这里，我们证明了基于DNA的疫苗，编码同基因或同种异体NKG 2D配体与肿瘤抗原，如生存素或癌胚抗原，显着激活先天性和适应性抗肿瘤免疫。这种疫苗在预防和治疗环境中产生高度有效的NK-和CD 8（+）T细胞介导的针对乳腺癌或结肠癌细胞的保护。值得注意的是，这种保护与肿瘤细胞的NKG 2D配体表达水平无关。因此，这种策略有可能导致广泛适用的和可能临床上有用的基于DNA的癌症疫苗。
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.