• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2004 Fiscal Year Final Research Report Summary

Anticancer therapy by hybrids of dendritic cells and interferon-α-overexpressing cells

Research Project

Project/Area Number 14570509
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionShowa University

Principal Investigator

HIROISHI Kazumasa  Showa University, University School of Medicine, Assistant Professor, 医学部, 講師 (80296996)

Project Period (FY) 2002 – 2004
Keywordsgene therapy / interferon-alpha / dendritic cell / immunotherapy / gastrointestinal cancer / hybrid / interleukin-4 / interleukin-12
Research Abstract

Dendritic cell (DC)-based immunotherapy has been used clinically against cancer although most attempts showed insufficient responses. Fusion technique for DCs and tumor cells has been developed and widely used in experimental models as well as clinical trials. To overcome an immunosuppressed state in patients with tumors, tumor-based vaccination in combination with cytokine gene therapy has also been used in treatment of these tumors. We previously showed the efficacy of IFN-α-overexpressing tumor in a murine poorly immunogenic colorectal cancer model. Therefore, we thought that immunotherapy using hybrids of DCs and IFN-α-overexpressing tumor cells might have more antitumor effects compared with therapy with hybrids of DCs and wild-type cells. In this study, we evaluated antitumor effects of therapy with hybrids of DCs and IFN-α gene transduced colorectal cancer cells in a murine model. We established an IFN-α-overexpressing MC38 colorectal cancer cell line (MC38-IFNα, producing 157.0 … More +-4.2 ng of IFN-α/10^6cells/48h) using a retroviral vector. We made hybrids of DCs and MC38-IFNα cells with polyethyleneglycol. To evaluate the preventive effects, the hybrids were injected in immunocompetent mice 7 days before injection of wild-type MC38 (MC38-WT). As a therapy against established tumors, hybrids were inoculated contralaterally 7 days after MC38-WT cells had been injected. Hybrids were detected 17-25% of the fused DCs and MC38-IFNα cells, and these cells produced a large amount of IFN-α. Preinjection of hybrids prevented implantation of wild-type tumors effectively in all mice. In the therapeutic model against established tumors, hybrids of DCs and MC38-IFNα cells suppressed growth of the tumors more effectively than hybrids of DCs and MC38-WT cells. Immunohistochemical analysis showed marked infiltration of CD8^+ cells in the established tumors of mice treated with hybrids of DCs and MC38-IFNα cells. Immunotherapy using hybrids of DCs and IFN-α-transduced tumor cells induces cellular antitumor immune response effectively, and should be considered in clinical trials. Less

  • Research Products

    (8 results)

All 2005 2003 2002

All Journal Article (8 results)

  • [Journal Article] Interleukin-4 gene transduced tumor cells promote a potent tumor-specific Th1-type response in cooperation with interferon-alpha transduction2005

    • Author(s)
      Junichi Eguchi, et al.
    • Journal Title

      Gene Therapy (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Interleukin-4 gene transduced tumor cells promote a potent tumor-specific Th-1 type response in cooperation with interferon-alpha transduction.2005

    • Author(s)
      Eguchi J, Hiroishi K, Ishii S, Baba T, Matsumura T, Hiraide A, Okada H, Imawari M
    • Journal Title

      Gene Ther.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Interferon-alpha and interleukin-12 gene therapy of cancer : interferon-alpha induces tumor-specific immune responses while interleukin-12 stimulates non-specific killing2003

    • Author(s)
      Junichi Eguchi, et al.
    • Journal Title

      Cancer Immunology and Immunotherapy 52

      Pages: 378-386

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Dendritic cell maturation induced by delivery of ultraviolet-mediated apoptotic colorectal cancer cell lines2003

    • Author(s)
      Shigeaki Ishii, et al.
    • Journal Title

      Anticancer Research 23(3B)

      Pages: 2457-2463

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Interferon-alpha and interleukin-12 gene therapy of cancer : interferon-alpha induces tumor-specific immune responses while interleukin-12 stimulates non-specific killing.2003

    • Author(s)
      Eguchi J, Hiroishi K, Ishii S, Mitamura K
    • Journal Title

      Cancer Immunol Immunother 52

      Pages: 378-386

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dendritic cell maturation induced by delivery of ultraviolet-mediated apoptotic colorectal cancer cell lines.2003

    • Author(s)
      Ishii S, Hiroishi K, Eguchi J, Mitamura K
    • Journal Title

      Anticancer Res 23(3B)

      Pages: 2457-2463

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Murine dendritic cell-induced tumor apoptosis is partially mediated by nitric oxide2002

    • Author(s)
      Hiromune Shimamura, et al.
    • Journal Title

      Journal of Immunotherapy 25

      Pages: 226-234

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Murine dendritic cell-induced tumor apoptosis is partially mediated by nitric oxide2002

    • Author(s)
      Shimamura H, Cumberland R, Hiroishi K, Watkins SC, Lotze MT, Baar J
    • Journal Title

      J Immunother 25

      Pages: 226-234

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2006-07-11  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi