A DNA vaccine targeting survivin combines apoptosis with suppression of angiogenesis in lung tumor eradication.
A DNA vaccine targeting survivin combines apoptosis with suppression of angiogenesis in lung tumor eradication.
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DOI：
10.1158/0008-5472.553.65.2
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发表时间：
2005-01
期刊：
影响因子：
11.2
通讯作者：
R. Xiang;N. Mizutani;Yunping Luo;C. Chiodoni;He Zhou;M. Mizutani;Y. Ba;J. Becker;R. Reisfeld
中科院分区：
文献类型：
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作者：
R. Xiang;N. Mizutani;Yunping Luo;C. Chiodoni;He Zhou;M. Mizutani;Y. Ba;J. Becker;R. Reisfeld
一种新的策略通过联合抑制肿瘤新生血管中的血管生成和诱导肿瘤细胞凋亡来实现肺肿瘤转移的根除。这是通过编码分泌性趋化因子CCL 21和凋亡抑制蛋白生存素的DNA疫苗诱导的CTL来实现的，所述蛋白生存素由肿瘤血管系统中的增殖内皮细胞和肿瘤细胞过度表达。通过双减毒鼠伤寒沙门氏菌（dam（-）和AroA（-））将该DNA疫苗口服递送至小肠中的派伊尔集合淋巴结等次级淋巴器官，引起抗原呈递树突状细胞的显著活化，以及针对生存素自身抗原的有效CD 8（+）T细胞免疫应答。这导致在C57 BL/6 J小鼠的预防性和治疗性环境中根除或抑制非小细胞肺癌的肺转移。此外，疫苗诱导的血管生成抑制不会损害伤口愈合或治疗小鼠的生育能力。预计这种新型DNA疫苗将有助于合理设计未来预防和治疗癌症的策略。
A novel strategy achieved the eradication of lung tumor metastases by joint suppression of angiogenesis in the tumor neovasculature and induction of tumor cell apoptosis. This was accomplished by CTLs induced by a DNA vaccine encoding secretory chemokine CCL21 and the inhibitor of apoptosis protein survivin, overexpressed by both proliferating endothelial cells in the tumor vasculature and tumor cells. Oral delivery of this DNA vaccine by doubly attenuated Salmonella typhimurium (dam(-) and AroA(-)) to such secondary lymphoid organs as Peyer's patches in the small intestine, elicited marked activation of antigen-presenting dendritic cells, and an effective CD8(+)T cell immune response against the survivin self-antigen. This resulted in eradication or suppression of pulmonary metastases of non-small cell lung carcinoma in both prophylactic and therapeutic settings in C57BL/6J mice. Moreover, the suppression of angiogenesis induced by the vaccine did not impair wound healing or fertility of treated mice. It is anticipated that such novel DNA vaccines will aid in the rational design of future strategies for the prevention and treatment of cancer.