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

Targeted gene therapy for incurable sarcoma using a novel replication-selective and oncolytic herpes virus harboring GM-CSF gene

Research Project

Project/Area Number 16591521
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionOsaka Medical Center for Cancer & Cardiovascular Diseases

Principal Investigator

YAMAMURA Hisako  Osaka Medical Center for Cancer & Cardiovascular Diseases, Department of Molecular Medicine, Associate director, 研究所, 主任研究員 (50342994)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Katsuhito  Osaka Medical Center for Cancer & Cardiovascular Diseases, Department of Molecular Medicine, Director, 研究所, 部長 (40211338)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordsherpes simplex virus / calponin / oncolytic virus / gene therapy / sarcoma / GM-CSF / GMP基準
Research Abstract

We have previously described a thymidme kinase (TK)-defective type I herpes simplex virus (HSV-1) mutant d12.CALP in which smooth muscle-specific calponin promoter drives expression of the RS1 gene encoding an essential trans-activating factor (ICP4) for viral genes (Yamamura et al. Cancer Res. 61; 3969-3977,2001). In order to improve efficacy and safety for pre-clinical and clinical testing, we have developed a new conditionally replicating oncolytic HSV-1 (d12.CALPΔRR GM-CSF) in which smooth muscle-specific calponin transcriptional regulatory sequence drives the RS1 gene and the human GM-CSF cDNA via bicistronic expression using the internal ribosomal entry site (IRES2). The engineered HSV-1 is a derivative of ICP4-null mutant d120 carrying the intact TK gene and an insertional mutation in the U_L39 gene encoding a large subunit of ribonucleotide reductase (ICP6), an essential enzyme for viral replication. d12.CALPΔRR GM-CSF also contains the Escherichia coli lacZ gene under the cont … More rol of the intrinsic U_L39 gene promoter to trace viral replication. We isolated three clones of the d12.CALPΔRR GM-CSF using limited dilution methods after infection to the SK-LMS-1 human leiomyosarcoma cells, following the selection of two cycles of infection to ICP4-transfected Vero cells. We also investigated the replication of the d12.CALPΔRR in ICP4-transfected Vero cells in serum free medium VP-SFM (Invitrogen), and successfully carried out a large scale viral purification using this medium. The sensitivity to GCV of the d12.CALPΔRR virus in VP-SFM was comparable to that in 10%FBS/DMEM medium. We further confirmed that replication of the d12.CALPΔRR virus in MethA fibrosarcoma cells in immuno-competent mice could induce MethA-specific anti-tumor immunity. We suggest that in addition to a direct oncolytic effects on the tumors, novel anti-leiomyosarcoma agents d12.CALPΔRR and d12.CALPΔRR GM-CSF may destroy sarcoma tumors in remote organs via systemic anti-tumor immunity, and thus should be investigated further as a challenging therapy for metastasis of incurable human sarcoma tumors Less

Report

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

    (7 results)

All 2006 2005

All Journal Article (6 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] 増殖型HSVベクターの開発-腫瘍溶解性ウイルスによる肉腫の標的遺伝子療法-2006

    • Author(s)
      高橋克仁, 山村倫子
    • Journal Title

      日本臨床 64

      Pages: 326-333

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Development of conditionally replicating oncolytic HSV vector ; targeted gene therapy for sarcoma by oncolytic viruses.2006

    • Author(s)
      Takahashi, K, Yamamura, H.
    • Journal Title

      Nippon Rinsho 64

      Pages: 326-333

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 骨・軟部腫瘍の遺伝子治療 : 肉腫破壊ウイルスによる細胞標的治療2005

    • Author(s)
      高橋克仁, 山村倫子
    • Journal Title

      NEW MOOK 整形外科 18

      Pages: 235-245

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene therapy fot bone and soft tissue tumors : A novel cell-targeting therapy by sarcoma-destructing virus.2005

    • Author(s)
      Takahashi, K, Yamamura, H.
    • Journal Title

      New Mook for Orthopaedic Surgery 18

      Pages: 235-245

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 難治性肉腫に対する新しい標的遺伝子治療法の開発2005

    • Author(s)
      高橋克仁, 山村倫子
    • Journal Title

      整形外科MOOK 5

      Pages: 670-678

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 骨・軟部腫瘍の遺伝子治療:肉腫破壊ウイルスによる細胞標的治療2005

    • Author(s)
      高橋克仁, 山村倫子
    • Journal Title

      整形外科 Vol.18(印刷中)

    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 血管新生制御方法2005

    • Inventor(s)
      高橋克仁, 山村倫子
    • Industrial Property Rights Holder
      大阪府
    • Filing Date
      2005-03-30
    • Related Report
      2005 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi