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Molecular characterization of sialylated HEG1, a specific targeting of tumor blood vessels

Research Project

Project/Area Number 19K07770
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionGunma University of Health and Welfare (2021-2022)
Kanagawa Cancer Center Research Institute (2019-2020)

Principal Investigator

Tsuji Shoutaro  群馬医療福祉大学, 医療技術学部, 教授 (30285192)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords腫瘍マーカー / 中皮腫 / 血管内皮細胞 / HEG1 / 腫瘍血管
Outline of Research at the Start

がん周囲の新生血管(腫瘍血管)はがん組織にがん細胞の増殖を促す。我々は抗HEG1抗体が腫瘍血管の内皮細胞に結合することを見いだした。本研究では、血管内皮細胞におけるHEG1の性状解析と腫瘍血管で特異的に起こるHEG1の糖鎖修飾の解析を行う。本研究によって、腫瘍血管に特異的な分子標的の性状が明らかとなり、新たな血管新生阻害剤の創製に貢献する。

Outline of Final Research Achievements

SKM9-2, a marker antibody for malignant mesothelioma, also binds to tumor blood vessels formed around cancer. This study revealed that SKM9-2 is a unique antibody that simultaneously recognizes sugar chains and peptides, and provided important findings for the development of new antibody drugs that target mesothelioma and tumor blood vessels. In addition, we were able to prove that the site-specific glycosylation of specific antigens, such as the epitope of SKM9-2, is useful for detecting and diagnosing diseases and abnormalities.

Academic Significance and Societal Importance of the Research Achievements

本研究によりSKM9-2が糖鎖とペプチドを同時認識するユニークな抗体であることが明らかとなった。研究成果は現在進行中のヒト化SKM9-2を用いた抗体治療薬開発において規制当局対応に関わる重要な知見となる。また、SKM9-2のエピトープで見られたような特定の抗原の部位に特異的な糖鎖付加は、疾患や異常の発見・診断に有用であることを立証することができ、部位特異的な糖鎖創薬という新たな医薬品開発の可能性を示すことができた。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (23 results)

All 2023 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (15 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results)

  • [Int'l Joint Research] Emory University(米国)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Medical application of the monoclonal antibody SKM9-2 against sialylated HEG1, a new precision marker for malignant mesothelioma2023

    • Author(s)
      TSUJI Shoutaro、IMAI Kohzoh
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 99 Issue: 2 Pages: 39-47

    • DOI

      10.2183/pjab.99.003

    • ISSN
      0386-2208, 1349-2896
    • Year and Date
      2023-02-10
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HEG1, BAP1, and MTAP Are Useful in Cytologic Diagnosis of Malignant Mesothelioma With Effusion.2021

    • Author(s)
      Hiroshima K, Wu D, Hamakawa S, Tsuruoka S, Ozaki D, Orikasa H, Hasegawa M, Koh E, Sekine Y, Yonemori Y, Nabeshima K, Tsuji S, Miyagi Y, Imai K.
    • Journal Title

      Diagn Cytopathol

      Volume: 49 Issue: 5 Pages: 622-632

    • DOI

      10.1002/dc.24475

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endogenous neurotoxin-like protein Ly6H inhibits alpha7 nicotinic acetylcholine receptor currents at the plasma membrane2020

    • Author(s)
      Moriwaki Yasuhiro、Kubo Natsuki、Watanabe Mizuho、Asano Shinsuke、Shinoda Tomoki、Sugino Taro、Ichikawa Daiju、Tsuji Shoutaro、Kato Fusao、Misawa Hidemi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 11996-11996

    • DOI

      10.1038/s41598-020-68947-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HEG1 is a Highly Specific and Sensitive Marker of Epithelioid Malignant Mesothelioma2020

    • Author(s)
      Naso Julia R.、Tsuji Shoutaro、Churg Andrew
    • Journal Title

      The American Journal of Surgical Pathology

      Volume: - Issue: 8 Pages: 1143-1148

    • DOI

      10.1097/pas.0000000000001469

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] HEG1-responsive microRNA-23b regulates cell proliferation in malignant mesothelioma cells2020

    • Author(s)
      Fujii Tomomi、Itami Hiroe、Uchiyama Tomoko、Morita Kohei、Nakai Tokiko、Hatakeyama Kinta、Sugimoto Aya、Shimada Keiji、Tsuji Shoutaro、Ohbayashi Chiho
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: - Issue: 4 Pages: 927-933

    • DOI

      10.1016/j.bbrc.2020.03.172

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 中皮腫の糖鎖修飾がん抗原を標的とする抗体医薬の開発2019

    • Author(s)
      辻 祥太郎
    • Journal Title

      Drug Delivery System

      Volume: 34 Pages: 284-290

    • Related Report
      2019 Research-status Report
  • [Journal Article] 新しい悪性中皮腫マーカー・シアル化HEG1による精密・早期診断の開発と臨床への展開2019

    • Author(s)
      辻 祥太郎、今井 浩三
    • Journal Title

      医学のあゆみ

      Volume: 271 Pages: 810-816

    • Related Report
      2019 Research-status Report
  • [Presentation] 悪性中皮腫の糖鎖修飾を認識する抗体と抗体医薬への展開2023

    • Author(s)
      辻 祥太郎
    • Organizer
      第74回日本電気泳動学会総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 糖ペプチド認識抗体SKM9-2の抗体医薬品への応用2021

    • Author(s)
      辻 祥太郎
    • Organizer
      第18回糖鎖科学コンソーシアムシンポジウム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 糖ペプチド認識抗体SKM9-2の結合構造解析.2021

    • Author(s)
      辻祥太郎, 千葉靖典, 久保田智巳.
    • Organizer
      第11回グライコバイオロジクス研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] Evaluation of cytotoxicity of bispecific antibody against mesothelioma.2020

    • Author(s)
      金守悠希, 森脇康博, 今井浩三, 辻祥太郎.
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 抗中皮腫効果を有する二重特異性抗体の開発2020

    • Author(s)
      金守悠希, 森脇康博, 三澤日出巳, 今井浩三, 辻祥太郎
    • Organizer
      第40回日本分子腫瘍マーカー研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] HEG1 is useful for cytologic diagnosis of malignant mesothelioma with serosal effusions.2019

    • Author(s)
      Hiroshima K, Wu D, Ozaki D, Hasegawa M, Koh E, Sekine Y, Tsuruoka S, Hamakawa S, Nabeshima K, Tsuji S, Miyagi Y, Imai K.
    • Organizer
      The Pulmonary Pathology Society Biennial Meeting in Dubrovnik
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ジオール結合タグを用いた回収型分子標的薬の開発.2019

    • Author(s)
      辻 祥太郎、今井 浩三
    • Organizer
      第70回日本電気泳動学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 血液中の中皮腫マーカー・HEG1を測定可能なsandwich ELISA系の構築2019

    • Author(s)
      加藤 嵩大、森脇 康博、三澤 日出巳、今井 浩三、辻 祥太郎
    • Organizer
      第39回日本分子腫瘍マーカー研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 悪性中皮腫抗原を標的としたキメラ抗原受容体の最適化2019

    • Author(s)
      紅露 拓、辻 祥太郎、今井 浩三、笹田 哲朗
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 抗中皮腫効果を有する二重特異性抗体2019

    • Author(s)
      金守 悠希、森脇 康博、三澤 日出巳、今井 浩三、辻 祥太郎
    • Organizer
      第10回グライコバイオロジクス研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 抗中皮腫効果を有する二重特異性抗体薬の開発2019

    • Author(s)
      金守 悠希、森脇 康博、 三澤日出巳、今井 浩三、辻 祥太郎
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 回収型分子標的薬・インテレクチン融合TNF受容体を用いた血中TNFの選択的除去2019

    • Author(s)
      小畑 翔太郎、森脇 康博、三澤 日出巳、辻 祥太郎
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 中皮腫の糖鎖修飾がん抗原を標的とする抗体医薬の開発2019

    • Author(s)
      辻 祥太郎
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 中皮腫がん抗原の探索と臨床への応用2019

    • Author(s)
      辻 祥太郎、今井 浩三
    • Organizer
      第1回日本石綿・中皮腫学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 新しい中皮腫マーカー抗体 SKM9-2 とその抗原・シアル化 HEG12019

    • Author(s)
      辻 祥太郎
    • Organizer
      第14回中皮腫細胞診セミナー
    • Related Report
      2019 Research-status Report
    • Invited

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Published: 2019-04-18   Modified: 2024-01-30  

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