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Development of technology to search for novel antibody targets by proteomics specialized on the surface of circulating tumor cells

Research Project

Project/Area Number 18H02004
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 34020:Analytical chemistry-related
Research InstitutionOsaka University

Principal Investigator

Inoue Tsuyoshi  大阪大学, 薬学研究科, 教授 (20263204)

Co-Investigator(Kenkyū-buntansha) 鎌田 春彦  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 創薬デザイン研究センター, プロジェクトリーダー (00324509)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords癌 / 抗体医薬 / 標的探索 / ストレプトアビジン / プロテオミクス / 血管内皮 / ビオチン化ラベル / 抗体医薬品 / 抗体開発 / 抗体標的探索 / 抗原探索 / 血中循環細胞 / ラベル化 / 質量分析 / 膜蛋白質 / 血中循環癌細胞
Outline of Final Research Achievements

Antibodies cannot penetrate directly into cells due to their molecular weight, and it is essential to develop a technology for the accurate analysis of membrane proteins that exist on the cell surface of diseased tissues. In this project, we established a technology to label membrane proteins with iminobiotinylated reagents and purify them using a modified streptavidin that shows specificity only for the labeled proteins.
By applying this labeling proteomics technology to a mouse model of cancer, we found that membrane protein transporter X was significantly upregulated in the vascular endothelium of metastatic cancer by comparison with wild-type mice, and that administration of the inhibitor had an antitumor effect on malignant lymphoma. This method was found to be an excellent technique for the discovery of new targets for the development of antibody drugs.

Academic Significance and Societal Importance of the Research Achievements

抗体は高い特異性と親和性を有し副作用が低いが、アンメットメディカルニーズを満たすほど標的分子はなく、新規標的探索技術の開発が望まれていた。特に抗体は分子量の問題から細胞内部には直接侵入できず、疾患部位の膜表在性蛋白質を高精度に分析できる技術の開発が必須となる。そこで非天然型ビオチンにのみ特異性を示す改変型ストレプトアビジンを用い、血液循環細胞表面をはじめラベル化された膜表在性蛋白質に特化したプロテオミクスにより新規標的蛋白質を効率よく発見して、アンメットメディカルニーズに応えた新規抗体医薬品を開発できる可能性が高く、非天然型ビオチン化試薬による新規探索技術の開発の意義は大きい。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (4 results)

All 2020 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Crown-ether-mediated crystal structures of the glycosyltransferase PaGT3 from Phytolacca americana2020

    • Author(s)
      Maharjan, R.; Fukuda, Y.; Nakayama, T.; Hamada, H.; Ozaki, S.; Inouem T.
    • Journal Title

      Acta Crystallographica Section D: Structural Biology

      Volume: 76 Issue: 6 Pages: 521-530

    • DOI

      10.1107/s2059798320005306

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure of cytochromeb5unique to tardigrades2020

    • Author(s)
      Fukuda Yohta、Kim JeeEun、Inoue Tsuyoshi
    • Journal Title

      Protein Science

      Volume: 29 Issue: 8 Pages: 1829-1835

    • DOI

      10.1002/pro.3896

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Patent(Industrial Property Rights)] ウテログロビンを構造基盤とする二重特異性ポリペプチド2019

    • Inventor(s)
      新山真由美、ほか11名
    • Industrial Property Rights Holder
      国立研究開発法人医薬基盤・健康・栄養研究所
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-044364
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗体医薬の開発に資する創薬標的タンパク質の同定方法及び標的タンパク質に対する抗体の製造方法2018

    • Inventor(s)
      鈴木常司、ほか8名
    • Industrial Property Rights Holder
      三井化学株式会社、ほか2社
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas

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Published: 2018-04-23   Modified: 2022-01-27  

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