Dendritic cells transduced with TEM8 recombinant adenovirus prevents hepatocellular carcinoma angiogenesis and inhibits cells growth

Abstract

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.