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Enhanced anti-tumor effects of herpes simplex virus thymidine kinase/ganciclovir system by codelivering monocyte chemoattractant protein-1 in hepatocellular carcinoma

Cancer Gene Therapy volume 8, pages 695–704 (2001)Cite this article

Abstract

The therapeutic efficacy of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system in many types of tumors is unsatisfactory due to the insufficient spread of gene transfer and insufficient cell killing. In the current study, we investigated whether adenovirally delivered monocyte chemoattractant protein (MCP)-1 potentiates the antitumor effects of the HSV-tk/GCV system in hepatocellular carcinoma (HCC) cells. Subcutaneous tumor foci of the human HCC cell line, HuH7, established in athymic mice were directly transduced with a recombinant adenovirus (rAd) harboring an HSV-tk gene driven by a human α-fetoprotein promoter, followed by GCV administration. Subsequently, another rAd expressing MCP-1 under the universal CAG promoter was injected. The growth of tumors was markedly suppressed by codelivering HSV-tk and MCP-1 genes compared to that by either HSV-tk/GCV or MCP-1 delivery. In the tumor tissues, monocyte/macrophage infiltration was detected immunohistochemically. The antitumor effects of the rAd expressing MCP-1 were markedly reduced by the administration of carrageenan, a compound known to inactivate macrophage. These results indicate that adenovirally delivered MCP-1 enhanced the antitumor effects of the HSV-tk/GCV system synergistically by recruitment/activation of macrophages in tumor tissues, suggesting an effective immunotherapy for HCC and other lineages of tumors when used adjuvantly with a suicide gene. Cancer Gene Therapy (2001) 8, 695–704

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Authors and Affiliations

  1. First Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan

    Yoshio Sakai, Shuichi Kaneko, Yasunari Nakamoto, Takashi Kagaya & Kenichi Kobayashi

  2. Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, 920-8641, Japan

    Naofumi Mukaida

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  1. Yoshio Sakai
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Correspondence to Shuichi Kaneko.

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Sakai, Y., Kaneko, S., Nakamoto, Y. et al. Enhanced anti-tumor effects of herpes simplex virus thymidine kinase/ganciclovir system by codelivering monocyte chemoattractant protein-1 in hepatocellular carcinoma. Cancer Gene Ther 8, 695–704 (2001). https://doi.org/10.1038/sj.cgt.7700360

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