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2004 Fiscal Year Final Research Report Summary

Effect of macrophages transduced with an adenoviral vector expressing interleukin-12 in prostate cancer

Research Project

Project/Area Number 15591712
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKitasato University

Principal Investigator

IWAMURA Masatsugu  Kitasato University, Medicine, Associate Professor, 医学部, 講師 (20176564)

Co-Investigator(Kenkyū-buntansha) SATOH Takefumi  Kitasato University, Medicine, Research associate, 医学部, 助手 (50286332)
IRIE Akira  Kitasato University, Medicine, Assistant Professor, 医学部, 講師 (50193694)
MATSUMOTO Kazumasa  Kitasato University, Medicine, Research associate, 医学部, 助手 (70306603)
Project Period (FY) 2003 – 2004
KeywordsInterleukin-12 / Macrophages / Prostate cancer / Immunomofulatory approaches / 米国
Research Abstract

For advanced prostate cancer, the standard therapy is androgen ablation, which largely palliative and it is critical to develop additional therapies that are effective against systemic disease to complement current treatments for localized prostate cancer. Novel approaches, such as immunogene therapy, provide opportunities to achieve these goals.
We investigated the efficacy of macrophages transduced with murine IL-12 recombinant adenoviral vector (AdmIL-12) using the 178-2 BMA mouse prostate cancer model. AdmIL-12-transduced macrophages secreted IL-12 in vitro and there were no significant differences in cell number at any MOI. Uninfected macrophages and Adβgal-infected macrophages produced very low levels of IL-12 at 24h and 48h, whereas a dose- and time- dependent increase in secretion of mIL-12 was detected in the AdmIL-12-infected macrophages. Cytometric analysis showed that AdmIL-12-infected macrophages had an 2 fold increase in surface expression of MHC class I and II molecules and F4/80 antigen compared with uninfected macrophages. Adβgal-infected macrophages were similar to uninfected macrophages except that increased MHC class II expression was observed. According to these results, we have demonstrated successful genetic modification of murine peritoneal exudates macrophages with adenoviral vectors and this therapeutic approach may induced substantial systemic antitumor immunological responses, hopefully. For next step to determine possible therapeutic activities AdmIL-12 transduced macrophages, we are going to set up preclinical experiment using an orthotopic mouse model of metastatic prostate cancer.

  • Research Products

    (7 results)

All 2005 2004 Other

All Journal Article (7 results)

  • [Journal Article] In situ gene therapy for prostate cancer.2005

    • Author(s)
      Satoh T, Irie A, et al.
    • Journal Title

      Curr Gene Ther. Jan;5(1)

      Pages: 111-119

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] In situ gene therapy for prostate cancer.2005

    • Author(s)
      Satoh T, Irie A, et al.
    • Journal Title

      Curr Gene Ther.Jan 5(1)

      Pages: 111-119

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Laparoscopic pyeloplasty for ureteropelvic junction obatruction : Outcome of initial 12 procedures.2004

    • Author(s)
      Iwamura M, Soh S, et al.
    • Journal Title

      Int J Urol. 11

      Pages: 449-455

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Current statues of gene therapy for urological cancer.

    • Author(s)
      Matsumoto K, Irie A, et al.
    • Journal Title

      Gene Therapy in Cancer. (accepted)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Immunomodulatory gene therapy for prostate cancer : Current outcome and future directions.

    • Author(s)
      Satoh T, Iwamura M et al.
    • Journal Title

      TRANSWORLD RESEARCH NETWORK (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Current statues of gene therapy for urological cancer

    • Author(s)
      Matsumoto K, Irie A, et al.
    • Journal Title

      Gene Therapy in Cancer (accepted)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cancer core distribution in patients diagnosed by extended transperineal prostate biopsy.

    • Author(s)
      Satoh T, Matsumoto K et al.
    • Journal Title

      Urology (in press)

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

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Published: 2006-07-11  

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