Ras gene mutation or overexpression can lead to tumorigenesis in multiple kinds of cancer, including glioma. However, no drugs targeting Ras or its expression products have been approved for clinical application thus far. Adenoviral gene therapy is a promising method for the treatment of glioma. In this study, the human glioma cell line U251 was co-cultured with recombinant adenovirus KGHV500, and the anti-tumor effects of KGHV500 were determined by MTT, scratch test, Transwell invasion, and apoptosis assays. Then, KGHV500 was delivered via the intravenous injection of CIK cells into glioma xenografts. Tumor volume, ki67 proliferation index, apoptosis levels, and anti-p21Ras scFv expression were tested to evaluate targeting ability, anti-tumor efficacy, and safety. We found that the KGHV500 exhibited anti-tumor activity in U251 cells and increased the intracellular expression of anti-p21Ras scFv compared with that in the control groups. CIK cells delivered KGHV500 to U251 glioma cell xenografts and enhanced anti-tumor activity against glioma xenografts compared to that produced by the control treatment. In conclusion, targeting Ras is a useful therapeutic strategy for gliomas and other Ras-driven cancers, and the delivery of anti-p21Ras scFv by recombinant adenovirus and CIK cells may play an essential role in the therapy of Ras-driven cancers. Impact statement For glioma treatment, gene therapy/virotherapy approach is a promising candidate. The Ras gene is reported to play a vital role in the RAS/RAF/mitogen-activated protein kinase (MAPK) pathway in gliomas. Thus, targeting the Ras gene should be a reasonable potential therapeutic method for glioma. In the present study, we used cytokine-induced killer (CIK) cells as secondary vectors to systemically deliver recombinant adenovirus KGHV500 to glioma xenografts and investigated the anti-tumor efficiency of recombinant adenovirus KGHV500 in vitro and in vivo. Our results expand evidence that targeting Ras is a useful and potential therapeutic strategy for gliomas. We believe that anti-p21Ras scFv delivered by recombinant adenovirus and CIK cells may play an important role in the therapy of Ras-driven cancers.
Adenovirus-Platelet Interaction in Blood Causes Virus Sequestration to the Reticuloendothelial System of the Liver