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Monocyte chemoattractant protein-1 gene delivery enhances antitumor effects of herpes simplex virus thymidine kinase/ganciclovir system in a model of colon cancer

Cancer Gene Therapy volume 13, pages 357–366 (2006)Cite this article

Abstract

Suicide gene therapy using the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system is a well-characterized tool for cancer gene therapy; however, it does not yet exhibit sufficient efficacy to cure patients of malignancies. We have reported that adenovirally delivered monocyte chemoattractant protein (MCP)-1 augmented the antitumor effects of the HSV-tk/GCV system in an athymic nude mouse model. The current study, which uses an immunocompetent mouse model of colon cancer, was designed to evaluate the antitumor effects of MCP-1 gene delivery in conjunction with this suicide gene therapy system. Subcutaneous tumor foci were directly transduced with both recombinant adenoviruses (rAds) expressing an HSV-tk gene and either of the MCP-1, CD80 and LacZ genes, followed by GCV administration. The growth of tumors was markedly suppressed by codelivery of HSV-tk and MCP-1 genes, which was exclusively associated with the recruitment of monocytes/macrophages, T helper 1 (Th1) cytokine gene expression and cytotoxic activity of the splenocytes. Furthermore, the antitumor effects were more efficient than that obtained by the combination of HSV-tk and CD80 genes. These results suggest an immunomodulatory effect of MCP-1 in the context of suicide gene therapy of colon cancer via orchestration of innate and acquired immune responses.

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan

    T Kagaya, Y Nakamoto, Y Sakai, T Tsuchiyama & S Kaneko

  2. Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan

    H Yagita

  3. Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan

    N Mukaida

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  1. T Kagaya
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Correspondence to S Kaneko.

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Kagaya, T., Nakamoto, Y., Sakai, Y. et al. Monocyte chemoattractant protein-1 gene delivery enhances antitumor effects of herpes simplex virus thymidine kinase/ganciclovir system in a model of colon cancer. Cancer Gene Ther 13, 357–366 (2006). https://doi.org/10.1038/sj.cgt.7700908

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