Dendritic cells transduced with TEM8 recombinant adenovirus prevents hepatocellular carcinoma angiogenesis and inhibits cells growth
Dendritic cells transduced with TEM8 recombinant adenovirus prevents hepatocellular carcinoma angiogenesis and inhibits cells growth
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DOI：
10.1016/j.vaccine.2010.07.014
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发表时间：
2010-10-08
期刊：
影响因子：
5.5
通讯作者：
Hu, Zhangxue
中科院分区：
文献类型：
--
作者：
Yang, Xuemei;Zhu, Huaping;Hu, Zhangxue
近年来的研究表明，血管生成在肝细胞癌（HCC）的发生、发展中起着重要作用，因此以抗血管生成为靶点的治疗策略被认为是治疗HCC的有效方法。肿瘤内皮标志物8（tumor endothelial marker 8，TEM 8）是近年来发现的一种特异性表达于肿瘤内皮细胞的蛋白质。然而，基于TEM 8的肝癌抗血管生成治疗尚未见报道。本研究构建了TEM 8重组腺病毒，并将其转染DC。此外，将修饰的DC转移到BALB/c小鼠中，以确定用TEM 8转导的DC是否可以在体内引发有效的抗肿瘤免疫原性应答。结果表明，Ad-TEM 8转染的DC能有效诱导特异性CTL，分泌IFN-γ，杀伤肝癌细胞。此外，修饰的DC可以有效地保护BALB/c小鼠免受肝癌的致死性攻击，减少肿瘤生长，并通过降低肿瘤血管密度来延长小鼠寿命。这些数据表明，Ad-TEM 8修饰的DC可以通过破坏肿瘤血管系统来诱导抗肿瘤免疫，因此可以在临床应用中用作影响肿瘤发展的有效治疗策略。(C)2010爱思唯尔有限公司版权所有。
Recent evidence suggested that angiogenesis played a pivotal role in the development of hepatocellular carcinoma cells (HCC), thus the therapy strategy targeting antiangiogenesis has been regarded as promising method for HCC therapy. Tumor endothelial marker 8 (TEM8) is a recently described protein that is preferentially expressed within tumor endothelium. However, the antiangiogenesis therapy of HCC based on TEM8 has not been reported. In this study, the recombinant adenovirus encoding TEM8 was constructed, and the DCs were transduced with the Ad-TEM8. In addition, the modified DCs were transferred into the BALB/c mice to determine whether DCs transduced with TEM8 could elicit a potent antitumor immunogenic response in vivo. The results demonstrated that DCs transduced with Ad-TEM8 induced specific CTLs effectively, which could secrete IFN-gamma and lyse HCC. Furthermore, the modified DCs could effectively protect BALB/c mice from lethal challenges against HCC, reduce tumor growth and increase the mice life span by decreasing tumor vasculature density. These data suggest that the Ad-TEM8 modified DCs may induce antitumor immunity by disrupting tumor vasculature and may thus be used as an efficient therapy strategy to influence tumor development in clinical applications. (C) 2010 Elsevier Ltd. All rights reserved.