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Development of cell and gene therapy for prostate cancer with dendritic cells engineered to produce interleukin-12

Research Project

Project/Area Number 16591596
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SAIKA Takashi  Okayama University, University Hospital of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 講師 (10314676)

Co-Investigator(Kenkyū-buntansha) NASU Yasutomo  Okayama University, Graduate School of Medicine, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20237572)
MANABE Daisuke  Okayama University, University Hospital of Medicine and Dentistry, Senior resident, 医学部・歯学部附属病院, 医員 (90379793)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsDendritic cell / Gene therapy / cancer immunology / Interleukin-12 / Prostate Cancer
Research Abstract

Bone marrow-derived DC were genetically engineered to express high levels of interleukin-12 (IL-12) with or without the costimulatory molecule B7-1, by ex vivo infection with recombinant adenoviral vectors. We used an orthotopic metastatic mouse prostate cancer preclinical model to compare two therapeutic protocols for DC delivery, in situ and subcutaneous. In vitro DC/IL-12 or DC/IL-12/B7 produced high levels of biologically active IL-12. In situ delivery of DC/IL-12 or DC/IL-12/B7 induced a significant suppression of primary tumor growth compared to DC/beta gal controls, as well as reduced numbers of spontaneous lung metastatic nodules. In survival experiments, in situ DC/IL-12 injection demonstrated a significant advantage. Subcutaneous, tumor lysate pulsed DC/IL-12 significantly decreased tumor size and increased survival compared to HBSS controls but the decrease in the number of spontaneous lung metastases did not achieve statistical significance. Both in situ and subcutaneous treatments enhanced cytolytic activities of natural killer (NK) cells and cytotoxic T lymphocytes (CTL). In this preclinical model, gene-modified DC-based intratumoral immunotherapy was shown to be an effective therapeutic strategy for locally advanced prostate cancer based on tumor growth suppression, inhibition of metastasis and survival improvement.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (5 results)

All 2006 2004

All Journal Article (5 results)

  • [Journal Article] Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model.2006

    • Author(s)
      Saika T et al.
    • Journal Title

      Cancer Gene Therapy 13・1

      Pages: 91-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model.2006

    • Author(s)
      Saika T et al.
    • Journal Title

      Cancer Gene Ther. 13(1)

      Pages: 91-98

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Route of administration influences the antitumor effects of bone marrow-derived dendritic cells engineered to produce interleukin-12 in a metastatic mouse prostate cancer model2004

    • Author(s)
      Saika T et al.
    • Journal Title

      Cancer Gene Therapy 11・5

      Pages: 317-24

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Route of administration influences the antitumor effects of bone marrow-derived dendritic cells engineered to produce interleukin-12 in a metastatic mouse prostate cancer model2004

    • Author(s)
      Saika T et al.
    • Journal Title

      Cancer Gene Therapy 11(5)

      Pages: 317-324

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Route of administration influences the antitumor effects of bone marrow-derived dendritic cells engineered to produce interleukin-12 in a metastatic mouse prostate cancer model2004

    • Author(s)
      Saika T
    • Journal Title

      Cancer Gene Therapy 11・5

      Pages: 317-324

    • Related Report
      2004 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

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