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Boron Drug Development to Expand the Indication of Boron Neutron Capture Therapy to Refractory Non-neoplastic Diseases

Research Project

Project/Area Number 21K15805
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionKyoto University

Principal Investigator

Watanabe Tsubasa  京都大学, 複合原子力科学研究所, 特定准教授 (30804348)

Project Period (FY) 2021-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsホウ素中性子捕捉療法
Outline of Research at the Start

ホウ素中性子捕捉療法とは中性子をホウ素原子が取り込み起こる核反応を用いて、正常組織にはほとんど影響を与えず病気にのみ放射線を照射する治療法です。これまでホウ素中性子捕捉療法は多くの方が困っている癌に対する治療として研究が進んできましたし、未ださらに癌をより良く治療できるようにホウ素中性子捕捉療法の領域で研究開発が進んでいます。しかし、人間の病気は癌だけではなく、癌以外にもなかなか治らずに苦しい思いをする疾患も多くあり、癌も他の難治性疾患も等しく人類の敵です。この研究では癌治療として発展してきたホウ素中性子捕捉療法を難治性の他疾患にも適応できるようにするための技術基盤を開発したいと考えています。

Outline of Final Research Achievements

Approximately 3.8 modules could be bound per antibody molecule (approximately 46 boron atoms per antibody molecule). For proof of concept, we first targeted CD8+ T cells, which can be easily extracted, and isolated CD8+ T cells from mouse spleens. The expression of CD8a protein in CD8+ T cells is 90,000, which is less than the amount of normal protein, and a theoretical 3% probability of boron neutron capture reaction occurs. The apoptosis after neutron irradiation was evaluated using flow cytometer RNA measurement, and an average increase of 2.8% of apoptotic cells was observed, which was almost consistent with the theoretical value.

Academic Significance and Societal Importance of the Research Achievements

既報のホウ素化抗体は、結合させられるホウ素クラスターの量が少なかったが、今回我々が開発したホウ素化モジュールによる抗体のホウ素化により抗体の抗原認識を損ねることなくより多くのホウ素原子を抗体に結合させることができた。ホウ素中性子捕捉療法は現在アミノ酸誘導体を主体としたホウ素薬剤のみが臨床応用可能であるが、抗体を用いた任意の細胞に対するホウ素原子の送達が可能となれば、ホウ素中性子捕捉療法の対象疾患を拡大することができる。今後、本モジュールのさらなる改良を目指し、より多くのホウ素原子を薬物送達の担体となる抗体へ結合させ、臨床応用の可能性を検討する。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (5 results)

All 2023 2022

All Journal Article (5 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results)

  • [Journal Article] Multi-Targeted Neutron Capture Therapy Combined with an 18 kDa Translocator Protein-Targeted Boron Compound Is an Effective Strategy in a Rat Brain Tumor Model2023

    • Author(s)
      Kashiwagi Hideki、Hattori Yoshihide、Kawabata Shinji、Kayama Ryo、Yoshimura Kohei、Fukuo Yusuke、Kanemitsu Takuya、Shiba Hiroyuki、Hiramatsu Ryo、Takami Toshihiro、Takata Takushi、Tanaka Hiroki、Watanabe Tsubasa、Suzuki Minoru、Hu Naonori、Miyatake Shin-Ichi、Kirihata Mitsunori、Wanibuchi Masahiko
    • Journal Title

      Cancers

      Volume: 15 Issue: 4 Pages: 1034-1034

    • DOI

      10.3390/cancers15041034

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The mutual relationship between the host immune system and radiotherapy: stimulating the action of immune cells by irradiation2022

    • Author(s)
      Watanabe Tsubasa、Sato Genki Edward、Yoshimura Michio、Suzuki Minoru、Mizowaki Takashi
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 28 Issue: 2 Pages: 201-208

    • DOI

      10.1007/s10147-022-02172-2

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Anti-tumor effect of boron neutron capture therapy in pelvic human colorectal cancer in a mouse model2022

    • Author(s)
      Arima Jun、Taniguchi Kohei、Yamamoto Masashi、Watanabe Tsubasa、Suzuki Yusuke、Hamamoto Hiroki、Inomata Yosuke、Kashiwagi Hideki、Kawabata Shinji、Tanaka Keitaro、Uchiyama Kazuhisa、Suzuki Minoru、Lee Sang-Woong
    • Journal Title

      Biomedicine & Pharmacotherapy

      Volume: 154 Pages: 113632-113632

    • DOI

      10.1016/j.biopha.2022.113632

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Correlation between the expression of LAT1 in cancer cells and the potential efficacy of boron neutron capture therapy2022

    • Author(s)
      Watanabe Tsubasa、Sanada Yu、Hattori Yoshihide、Suzuki Minoru
    • Journal Title

      Journal of Radiation Research

      Volume: 64 Issue: 1 Pages: 91-98

    • DOI

      10.1093/jrr/rrac077

    • Related Report
      2022 Annual Research Report
  • [Journal Article] The mutual relationship between the host immune system and radiotherapy2022

    • Author(s)
      Tsubasa Watanabe, Genki Edward Sato, Michio Yoshimura, Minoru Suzuki, Takashi Mizowaki
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 0 Pages: 0-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed

URL: 

Published: 2021-04-28   Modified: 2024-01-30  

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