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Regulation for multidrug resistant cancer and cancer stem cells by ABC transporter-targeted virus

Research Project

Project/Area Number 18590315
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human genetics
Research InstitutionThe University of Tokyo (2007)
Kurume University (2006)

Principal Investigator

NAKANO Kenji  The University of Tokyo, Institute of Medical Science, Associate Professor (00315061)

Co-Investigator(Kenkyū-buntansha) KOHNO Kimitoshi  University of Occupational and Environmental Health, School of Medicine, 医学部, Professor (00153479)
YAMANA Hideaki  University of Kurume, School of Medicine, Professor (30140669)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsAntibody derivatives / Targeting / EGFR / HSV / Cancer / Gene therapy / がん治療 / 癌治療
Research Abstract

The purpose of current study was to examine the specificity and efficacy of targeted therapeutic molecule for EGFR-overexpressing cancer cells, in stead of ABCG2-positive cancer stem cells due to technical difficulty in culture.
1) Comparison for targeting ligand of single chain of antibody against EGFR versus EGF
We constructed two types of adapters comprising of nectin1-V-domain fused to a single chain of antibody (scFv) against EGFR or a natural ligand, EGF. The efficacy of adapter-mediated HSV infection was significantly higher when HSV was challenged with the scFv-adapters than EGF-adapters. The potential factors for the differential entry efficiency seem to be the followings.
a) The scFv-adapter had a higher affinity to HSV-gD than EGF-adapter although the affinity to EGFR was similar.
b) The scFv-adapter did not induce the activation of EGFR so much as the EGF-adapter.
c) The EGF-adapter was rapidly degraded in endosome-lysosome pathway, whereas the scFv-adapter was resistant at the … More same time points by 30 min post-binding.
The scFv-adapter is superior to the EGF-adapter as a targeting ligand for EGFR-mediated HSV infection. (Under manuscript preparation)
2) Efficacy of EGFR-targeted suicide gene therapy
We constructed the expression plasmid for EGFR scFv-fused to E. coli PNP suicide gene and CA19-9 scFv-fused to E. coli PNP as the control, and then established colon cancer cell lines stably expressing the suicide genes. The efficacy of targeted suicide gene therapy for EGFR-overexpressing cancer was compared between the two targeting ligands. Tumor growth was more inhibited by the both suicide gene therapies compared with the saline control. EGFR scFv-fused to PNP suicide gene therapy induced a complete regression in some of mice harboring subcutaneous EGFR-overexpressing colon cancer and exhibited higher therapeutic efficacy than the control of CA19-9 scFv-fused suicide gene therapy. Immnofluorescence staining showed the co-localization of suicide gene expression and tumor vessels when provided with EGFR scFv-fused suicide gene but not much with CA 19-9 scFv-fused suicide gene (Biotherapy 21; 229-34, 2007) Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (11 results)

All 2008 2007 2006

All Journal Article (7 results) (of which Peer Reviewed: 1 results) Presentation (3 results) Book (1 results)

  • [Journal Article] 癌に対するウイルス・遺伝子治療の現状と展望2008

    • Author(s)
      中野賢二, 田原秀晃
    • Journal Title

      医事新報 4639

      Pages: 65-68

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of Erb2/HER2 and Estrogen receptor alpha depends upon nuclear localization of Y-box binding protein-1 in human breast cancers.2008

    • Author(s)
      Fujii T, Kawahara A, Basaki Y, Hattori S, Nakashima K, Nakano K, Shirouzu K, Kohno K, Yanagawa T, Yamana H, Nishio K, Ono M, Kuwano M, Kage M
    • Journal Title

      Cancer Res 68

      Pages: 1504-1512

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Current status and perspective of viro- and gene therapy for cancer2008

    • Author(s)
      Nakano K, Tahara H.
    • Journal Title

      Japan Medical Journal 4639

      Pages: 65-68

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 癌に対するウイルス・遺伝子治療の現状と展望2008

    • Author(s)
      中野賢二、田原秀晃
    • Journal Title

      医事新報 4639

      Pages: 65-68

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 抗体分子・細胞デリバリーシステムの標的化がん治療への応用2007

    • Author(s)
      中野賢二
    • Journal Title

      Biotherapy 21

      Pages: 229-234

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Journal Article] Application of antibody derivatives and cell-based delivery system for targeting molecule and bio-therapy2007

    • Author(s)
      Nakano K.
    • Journal Title

      Biotherapy 21

      Pages: 229-34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 腫瘍溶解性ヘルペスウイルスの癌治療への応用2006

    • Author(s)
      中野 賢二
    • Journal Title

      医学のあゆみ 216・8

      Pages: 615-616

    • Related Report
      2006 Annual Research Report
  • [Presentation] 抗体分子vs EGFリガンド : EGFRに対する標的化分子としての有用性の比較2008

    • Author(s)
      中野賢二, 田原秀晃
    • Organizer
      第67回日本癌学会総会(Workshop)
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] scFv versus EGF ligand: comparative study for targeting molecule against EGFR (Workshop)2008

    • Author(s)
      Nakano K.
    • Organizer
      67^<th> Annual Meeting of Japanese Cancer Association
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-10-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 抗体分子 vs EGFリガンド:EGFRに対する標的化分子としての有用性の比較2008

    • Author(s)
      中野賢二, 田原秀晃
    • Organizer
      第67回日本癌学会総会(Workshop)
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-29
    • Related Report
      2007 Annual Research Report
  • [Book] 消化器がん 化学療法 2006 「消化器がんにおける分子標的治療」2006

    • Author(s)
      中野賢二, 藤井輝彦, 山名秀明, 桑野信彦
    • Publisher
      日本メディカルセンター
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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