Respiratory Department of Daping Hospital, Third Military, Medical University, Chongqing 400042, China.
Vaccine. 2010 Oct 8;28(43):7130-5. doi: 10.1016/j.vaccine.2010.07.014. Epub 2010 Sep 16.
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-γ 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.
最近的证据表明，血管生成在肝细胞癌（HCC）细胞的发展中起着关键作用，因此针对抗血管生成的治疗策略被认为是 HCC 治疗的有前途的方法。肿瘤内皮标志物 8（TEM8）是最近描述的一种蛋白，它在肿瘤内皮中优先表达。然而，基于 TEM8 的 HCC 抗血管生成治疗尚未报道。在这项研究中，构建了编码 TEM8 的重组腺病毒，并将 Ad-TEM8 转导至 DC 中。此外，将修饰后的 DC 转移到 BALB/c 小鼠中，以确定转导 TEM8 的 DC 是否可以在体内引发有效的抗肿瘤免疫应答。结果表明，转导 Ad-TEM8 的 DC 可有效诱导特异性 CTL，其可分泌 IFN-γ并裂解 HCC。此外，修饰后的 DC 可有效保护 BALB/c 小鼠免受致命的 HCC 挑战，通过减少肿瘤血管密度来抑制肿瘤生长并延长小鼠的寿命。这些数据表明，Ad-TEM8 修饰的 DC 可通过破坏肿瘤血管来诱导抗肿瘤免疫，因此可作为一种有效的治疗策略，在临床应用中影响肿瘤的发展。
