DNA Vaccine Against Tumor Endothelial Marker 8 Inhibits Tumor Angiogenesis and Growth
DNA Vaccine Against Tumor Endothelial Marker 8 Inhibits Tumor Angiogenesis and Growth
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针对肿瘤内皮标记物 8 的 DNA 疫苗抑制肿瘤血管生成和生长
DOI：
10.1097/cji.0b013e3181a1d134
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发表时间：
2009-06-01
影响因子：
3.9
通讯作者：
Wu, Yuzhang
中科院分区：
文献类型：
--
作者：
Ruan, Zhihua;Yang, Zhao;Wu, Yuzhang
大量证据表明血管生成是肿瘤发展的关键步骤，因此抗血管生成的免疫治疗已成为癌症免疫治疗的潜在相关候选靶点。近年来，肿瘤内皮标志物8 （tumor endothelial marker 8, TEM8）被发现在肿瘤内皮中显性表达，为抗血管生成治疗提供了一种新的策略。然而，到目前为止，TEM8抗血管生成的相关研究还很少。在本研究中，我们构建了一种由减毒鼠伤寒沙门菌携带的人TEM8基因编码的异种DNA疫苗。结果表明，口服这种异种疫苗克服了外周免疫耐受，产生了tem8特异性CD8（+）细胞毒性t细胞应答。此外，该疫苗有效地保护小鼠免受肿瘤细胞的致命攻击，减少肿瘤生长，延长小鼠寿命。同时抑制肿瘤血管生成，无明显副作用。这些结果表明，编码异种TEM8的DNA疫苗可能作为肿瘤抗血管生成免疫治疗的潜在策略。
Numerous evidences indicated that angiogenesis was a crucial step in the development of tumor, thus the immunotherapy of antiangiogenesis has been involved as potentially relevant candidate targets of cancer immunotherapy. Recently, tumor endothelial marker 8 (TEM8) was discovered to be dominantly expressed in tumor endothelium, which presented a new strategy to antiangiogenesis therapy. However, up to date, the related study of TEM8 on antiangiogenesis is very few. In this Study, we constructed a xenogenic DNA vaccine encoding human TEM8 carried by attenuated Salmonella typhimurium. The results demonstrated that oral administration of this xenogenic vaccine Overcame peripheral immune tolerance and generated TEM8-specific CD8(+) cytotoxic T-cell response. Moreover, this vaccine effectively protected mice from lethal challenges against tumor cells, reducing tumor growth, and increasing the mice life span. In addition, angiogenesis in the tumors was Suppressed without obvious side effect. These results indicated that DNA vaccine encoding xenogenic TEM8 might act as a potential strategy for antiangio-genesis immunotherapy of tumors.