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Development of novel tumor specific molecule-based dual combination therapy: radioimmunotherapy and photoimmunotherapy in pancreatic tumor model

Research Project

Project/Area Number 17K10460
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionNational Institutes for Quantum and Radiological Science and Technology

Principal Investigator

Aung U.Winn  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 分子イメージング診断治療研究部, 主任研究員(任常) (70392214)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords膵臓 / 光免疫療法 / 核医学(PETを含む) / 蛍光イメージング / 分子イメージング / 膵癌 / 放射免疫療法
Outline of Final Research Achievements

Pancreatic cancer is one of the most incurable malignancy. A possible solution might come from the appropriate combinatory application of the new treatment modalities: targeted photoimmunotherapy (PIT), radioimmunotherapy (RIT), and chemotherapy. The purpose of study is to develop the novel antibody-based dual-modality therapy in pancreatic tumor model. We targeted the molecules that show high expression in pancreatic cancer. We performed tumor-specific antigen (integrin α6β4)-targeted RIT combined with BEZ235 (PI3K/mTOR inhibitor) administration and proved that combination therapy has higher therapeutic effect than RIT alone. Unfortunately, we couldn't develop a new dual-labeled antibody (Anti-α6β4) with both a radioisotope and a fluorescent moiety. Then, we investigated the other alternative targeted molecules and antibodies for PIT and showed that Anti-tissue factor antibody and Human epidermal growth factor receptor 2 antibody are potentially useful for effective PIT.

Academic Significance and Societal Importance of the Research Achievements

難治性がんである膵臓がんの予後は悪い内、治療選択肢はまだ制限されている。外科手術、アジュバント化学療法と放射線療法などは、満足な結果を与えるのに十分ではない。新しい治療法である光免疫療法(Photoimmunotherapy(PIT))を放射免疫療法(Radioimmunotherapy(RIT))又は化学療法などと適切に融合することによる新しい膵癌治療法の開発が解決に繋がる可能性があると考えられる。本研究では、膵癌で高発現している分子を標的する抗体に蛍光部分や放射性同位元素を標識したのを用いて療法を行い、効果を前臨床段階で評価した。将来的に臨床に応用できる可能性があると結論できた。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Anti-tissue factor antibody?mediated immuno?SPECT imaging of tissue factor expression in mouse models of pancreatic cancer2019

    • Author(s)
      Sugyo Aya、Aung Winn、Tsuji Atsushi、Sudo Hitomi、Takashima Hiroki、Yasunaga Masahiro、Matsumura Yasuhiro、Saga Tsuneo、Higashi Tatsuya
    • Journal Title

      Oncology Reports

      Volume: 41 (4) Pages: 2371-2378

    • DOI

      10.3892/or.2019.7017

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Near-infrared photoimmunotherapy of pancreatic cancer using an indocyanine green-labeled anti-tissue factor antibody2018

    • Author(s)
      Aung Winn、Tsuji Atsushi B、Sugyo Aya、Takashima Hiroki、Yasunaga Masahiro、Matsumura Yasuhiro、Higashi Tatsuya
    • Journal Title

      World Journal of Gastroenterology

      Volume: 24 (48) Issue: 48 Pages: 5491-5504

    • DOI

      10.3748/wjg.v24.i48.5491

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/mTOR inhibitor2017

    • Author(s)
      Aung Winn、Tsuji Atsushi B、Sudo Hitomi、Sugyo Aya、Ukai Yoshinori、Kouda Katsushi、Kurosawa Yoshikazu、Furukawa Takako、Saga Tsuneo、Higashi Tatsuya
    • Journal Title

      World Journal of Gastroenterology

      Volume: 23 (42) Issue: 42 Pages: 7551-7562

    • DOI

      10.3748/wjg.v23.i42.7551

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Current status of photoimmunotherapy (the cousin of radioimmunotherapy) in cancer management2019

    • Author(s)
      Winn Aung
    • Organizer
      Second National Conference of Myanmar Nuclear Medicine Society, Yangon, Myanmar
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Near-infrared Photoimmunotherapy Targeting Pancreatic Cancer With Tissue Factor Antibody2018

    • Author(s)
      1.Winn Aung, Atsushi Tsuji, Aya Sugyou, Hiroki Takashima, Masahiro Yasunaga, Yasuhiro Matsumura, Tatsuya Higashi
    • Organizer
      31th Annual Congress of the European Association of Nuclear Medicine, European Association of Nuclear Medicine, Dusseldorf, Germany
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Multi-b and multi-diffusion-time DWIを用いた脳腫瘍マウスにおけるコンパートメ ント間水交換の定量的評価2018

    • Author(s)
      2.今泉 晶、小畠 隆行、須尭 綾、Winn Aung, 辻 厚至、立花 泰彦、Kershaw Jeffrey,青木 伊知男
    • Organizer
      第46回日本磁気共鳴医学会大会, 金沢, 日本
    • Related Report
      2018 Research-status Report
  • [Presentation] Improvement of therapeutic efficacy by combing 90Y-ITGA6B4-mediated radioimmunotherapy (RIT) with dual PI3K and mTOR inhibitor NVP-BEZ232017

    • Author(s)
      Winn Aung, Atsushi Tsuji, Hitomi Sudou, Aya Sugyou, Yoshinori Ukai, Katsushi Kouda, Yoshikazu Kurosawa, Takako Furukawa, Tsuneo Saga, Tatsuya Higashi
    • Organizer
      30th Annual Congress of the European Association of Nuclear Medicine, Vienna, Austria,
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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