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Targeting surface antigens for intraoperative treatment of IDH mutant gliomas

Research Project

Project/Area Number 17K16632
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionNiigata University

Principal Investigator

Natsumeda Manabu  新潟大学, 脳研究所, 助教 (00515728)

Research Collaborator KATO Yukinari  
ABE Hideaki  
OKADA Masayasu  
WATANABE Jun  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsグリオーマ / 神経膠腫 / NIR-PIT / 光線免疫療法 / 術中療法 / ポドプラニン / Glioma / IDH変異 / Podoplanin / IDH / 免疫療法 / 腫瘍イメージング / 腫瘍学 / 術中治療
Outline of Final Research Achievements

The present research was devoted to looking at the potential application of intraoperative antibody treatment targeting isocitrate dehydrogenase (IDH) mutant protein. We tested 4 IDH1-mutant antibodies (HMab1, HMab-2, H09, and MsMab-1) against 2 IDH-mutant glioma cell lines (MGG152, BT142) by flowcytometry and found that only 10-20% of cells stained weakly positive. These results suggested that IDH1-mutant protein was not a good target for near infrared photoimmunotherapy (NIR-PIT) in gliomas, probably because IDH1 mutation is expressed in the cytoplasm of IDH1-mutant gliomas and not the cell surface.
Next, we targeted podoplanin, a membrane bound antigen highly expressed in malignant gliomas by using 4 podoplanin antibodies against 2 podoplanin expressing cell lines, and found an almost 100% positivity by flow cytometry. NIR-PIT using podoplanin-IR700 conjugate induced blebbing and cell death in glioblastoma cell lines in vitro.

Academic Significance and Societal Importance of the Research Achievements

悪性神経膠腫は極めて予後の悪い脳腫瘍であり、その治療法の確立は急務である。周囲脳に細胞が浸潤し、手術で取り切れない。本研究は悪性神経膠腫に対して、近赤外線光線免疫療法(NIR-PIT)という、腫瘍細胞の表面抗原を標的し腫瘍細胞のみを破壊する抗原特異的免疫療法の確立を目指した。腫瘍特異抗体を蛍光標識することで術中の残存腫瘍の評価にも利用できることから、NIR-PITの実現は神経膠腫に革命的な治療の進歩をもたらす可能性を秘めている。細胞表面ではなく細胞質に発現するIDH1抗体によるNIR-PITは上手く行かなかったが、その後、ポドプラニンという細胞膜蛋白に対するNIR-PITの有効性が示唆された。

Report

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

    (8 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Podoplanin expression and IDH-wildtype status predicts venous thromboembolism in patients with high-grade gliomas in the early postoperative period.2019

    • Author(s)
      Watanabe J, Natsumeda M, Okada M, Kanemaru Y, Tsukamoto Y, Oishi M, Kakita A, Fujii Y.
    • Journal Title

      World Neurosurg.

      Volume: 印刷中 Pages: 2275-2281

    • DOI

      10.1016/j.wneu.2019.05.049

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] High detection rate of MYD88 mutations in cerebrospinal fluid from patients with central nervous system lymphomas2019

    • Author(s)
      Jun Watanabe, Manabu Natsumeda, Masayasu Okada, Daiki Kobayashi, Yu Kanemaru, Yoshihiro Tsukamoto, Makoto Oishi, Akiyoshi Kakita, Yukihiko Fujii
    • Journal Title

      JCO Precision Oncology

      Volume: 3 Issue: 3 Pages: 1-13

    • DOI

      10.1200/po.18.00308

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy.2018

    • Author(s)
      Natsumeda M, Motohashi K, Igarashi H, Nozawa T, Abe H, Tsukamoto Y, Ogura R, Okada M, Kobayashi T, Aoki H, Takahashi H, Kakita A, Okamoto K, Nakada T, Fujii Y.
    • Journal Title

      Neurosurg Rev

      Volume: 41 Issue: 2 Pages: 641-647

    • DOI

      10.1007/s10143-017-0908-y

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Advances and Challenges in Assessing 2-Hydroxyglutarate in Gliomas by Magnetic Resonance Spectroscopy: A Short Review2018

    • Author(s)
      Manabu Natsumeda, Hironaka Igarashi, Kunio Motohashi, Yuji Suzuki, Masaki Ohkubo, Kouichirou Okamoto, Masaki Watanabe, Tsutomu Nakada, Yukihiko Fujii
    • Journal Title

      Neuropsychiatry (London)

      Volume: 8 Pages: 739-744

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 悪性神経膠腫の新規治療について ー光線力学療法の現状と展望ー2019

    • Author(s)
      棗田 学
    • Organizer
      第72回新潟脳神経外科懇話会
    • Related Report
      2018 Annual Research Report
  • [Presentation] IDH変異型グリオーマの診断と治療~コラボレーションを通して実現を目指す~2019

    • Author(s)
      棗田 学
    • Organizer
      第18回日本蛋白質学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] IDH変異グリオーマを標的とした 術中イメージング法・治療法確立の試み2017

    • Author(s)
      棗田 学
    • Organizer
      新潟PDT研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 臨床医が帰国後に研究を続けるためにとった術2017

    • Author(s)
      棗田 学
    • Organizer
      57th Meeting of Japanese Society for Science in Baltimore
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2020-03-30  

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