@article{oai:kanazawa-u.repo.nii.ac.jp:00013710, author = {Marukawa, Yohei and Nakamoto, Yasunari and Kakinoki, Kaheita and Tsuchiyama, Tomoya and Iida, Noriho and Kagaya, Takashi and Sakai, Yoshio and Naito, Makoto and Mukaida, Naofumi and Kaneko, Shuichi}, issue = {5}, journal = {Cancer Gene Therapy}, month = {May}, note = {Suicide gene therapy using the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system combined with monocyte chemoattractant protein-1 (MCP-1) provides significant antitumor efficacy. The current study was designed to evaluate the antitumor immunity of a newly developed membrane-bound form of MCP-1 (mMCP-1) in an immunocompetent mouse model of hepatocellular carcinoma (HCC). A recombinant adenovirus vector (rAd) harboring the human MCP-1 gene and the membrane-spanning domain of the CX3CL1 gene was used. Large amounts of MCP-1 protein were expressed and accumulated on the tumor cell surface. The growth of subcutaneous tumors was markedly suppressed when tumors were treated with mMCP-1, as compared with soluble MCP-1, in combination with the HSV-tk/GCV system (P<0.01). The numbers of Mac-1-, CD4- and CD8a-positive cells were significantly higher in tumor tissues (P<0.05), and tumor necrosis factor (TNF) mRNA expression levels with mMCP-1 were almost five-fold higher than those with soluble MCP-1. These results indicate that the delivery of the mMCP-1 gene greatly enhanced antitumor effects following the apoptotic stimuli by promoting the recruitment and activation of macrophages and T lymphocytes, suggesting a novel strategy of immune-based gene therapy in the treatment of patients with HCC.Cancer Gene Therapy advance online publication, 9 March 2012; doi:10.1038/cgt.2012.3.}, pages = {312--319}, title = {Membrane-bound form of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy in a model of hepatocellular carcinoma}, volume = {19}, year = {2012} }