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Development of cancer therapeutic strategies targeting for extracellular matrix CSPG4.

Research Project

Project/Area Number 16K08375
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

ITOH Kunihiko  静岡県立大学, 薬学部, 教授 (90221770)

Co-Investigator(Kenkyū-buntansha) 井上 和幸  静岡県立大学, 薬学部, 准教授 (90514589)
辻 大樹  静岡県立大学, 薬学部, 講師 (90565615)
平井 啓太  静岡県立大学, 薬学部, 助教 (30740203)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsCSPG4 / がん分子標的治療 / 抗体医薬 / 細胞外マトリクス / がん免疫組織化学 / IgG / すい臓がん / 乳がん / 悪性中皮腫 / ADCC活性 / リコンビナントFab / メラノーマ / 細胞外マトリックス / ヒト型抗体 / エピトープペプチド
Outline of Final Research Achievements

While extracellular matrix CSPG4 is expressed in many cancer types, its expression at normal sites is limited and promising as a cancer therapeutic target. In the present study, anti-CSPG4rFab isolated by the applicant was expressed as a complete IgG, and ADCC activity to CSPG4 expressing cancer cells was confirmed. In addition, immunohistochemistry revealed that CSPG4 is highly expressed in malignant melanoma and breast cancer tissues. Particularly in breast cancer, it was revealed that CSPG4 is highly expressed in also triple negative breast cancer. Although the expected results were not obtained for anti-CSPG4 antibody induction by the epitope peptide immunization, this study has shown the utility of CSPG4 as a tumor diagnostic and therapeutic targets.

Academic Significance and Societal Importance of the Research Achievements

申請者が単離した抗CSPG4rFabより作製した完全IgGが、CSPG4陽性細胞に対してADCC活性を示したことから、がん治療に有用な医薬品として開発可能であることが明らかとなった。また、CSPG4が、悪性黒色腫および乳がんの診断マーカーとして有用であり、治療抵抗性であるトリプルネガティブ乳がんにもCSPG4が高発現していることから治療標的としても有用であることを明らかにした。本研究の学術的意義は、CSPG4のがん診断や治療における有用性を新たに確認できた点にあり、社会的意義は、臨床における新たながん治療戦略としてのCSPG4分子標的治療を提案できた点にあると考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (4 results)

  • [Journal Article] Human recombinant Fab fragment from combinatorial libraries of a B-cell lymphoma patient recognizes core protein of chondroitin sulphate proteoglycan 4.2018

    • Author(s)
      Egami Y, Narushima Y, Ohshima M, Yoshida A, Yoneta N, Masaki Y, Itoh K.
    • Journal Title

      J Biochem.

      Volume: 163 Issue: 1 Pages: 61-68

    • DOI

      10.1093/jb/mvx065

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 細胞外マトリックスCSPG4の各種がん組織での発現2019

    • Author(s)
      伊藤邦彦、志田幸平、青山春菜、鈴木詩絵里、平井啓太、吉村久志、石渡俊行
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SPG4 is a promising marker for immunohistochemical detection of breast cancer, including triple negative breast cancer2019

    • Author(s)
      Kunihiko Itoh, Keita Hirai, Hisashi Yoshimura, and Toshiyuki Ishiwata
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Establishment of complete human IgG antibody expression system from recombinant Fab against CSPG4 on tumor cells2018

    • Author(s)
      Kunihiko Itoh, Kouhei Shida, Haruna Aoyama, Shieri Suzuki
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗CSPG4完全ヒト型抗体発現系の構築と評価2018

    • Author(s)
      伊藤邦彦,志田幸平,青山春菜,鈴木詩絵里
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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