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難治性固形癌予後改善に資する間質バリアを克服するための新規放射免疫療法戦略の開発

Research Project

Project/Area Number 18H02774
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionNational Institutes for Quantum Science and Technology

Principal Investigator

辻 厚至  国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 分子イメージング診断治療研究部, グループリーダー (60303559)

Co-Investigator(Kenkyū-buntansha) 眞鍋 史乃  星薬科大学, 薬学部, 教授 (60300901)
安永 正浩  国立研究開発法人国立がん研究センター, 先端医療開発センター, 分野長 (80450576)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Granted (Fiscal Year 2022)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Keywords核医学治療 / RI治療
Outline of Annual Research Achievements

抗体を利用した放射免疫療法(Radioimmunotherapy, RIT)は,血液癌での臨床での有用性は示されているが,固形癌での有用性は,動物モデルのみで,臨床では未だ示されていない。この大きな原因のひとつは,血液癌と違い,固形癌では間質が非常に多く,薬剤到達を阻む間質バリアが存在するが,これを克服するRIT戦略が描けていないからである。そこで,固形癌に有効な新しいRIT戦略の確立を目的として研究を実施した。これまでに,癌間質を標的とする抗体をIn-111標識し,その性能評価を5種類の固形癌モデル腫瘍を形成させたマウスで実施した。これら5種類の固形癌モデルは癌間質やそれを誘導する生体分子の発現が異なる。放射性標識抗体を投与し,SPECT/CTイメージングおよび体内動態試験を実施した結果,癌間質が豊富な固形癌モデルに高集積することが明らかとなった。また癌間質形成に関わる分子の発現に相関することも明らかとした。癌間質が豊富な固形癌モデル腫瘍に高集積することは蛍光標識抗体でも実証した。治療用放射性核種に変えて抗体を投与した場合,腫瘍に40Gyを照射できると推定された。この癌間質が豊富な固形癌モデルはRITを始めとする各種抗癌治療に抵抗性を示すことも別実験で明らかにしており,今年度は,治療評価を実施した。抗体をβ線放出核種Y-90で標識し,間質が豊富な膵癌モデルに投与して治療効果を評価した。統計的有意に腫瘍増殖を抑制することを明らかにした。腫瘍縮小効果も見られ,これまでのち療法よりも効果が高いことが明らかとなった。膵癌治療法として有望であることが示された。さらなる治療効果を高めるために,リリース型ADCの開発に取り組んだ。リンカーを変えることで治療効果を高めることを見出した。併用療法の治療効果の評価を継続する。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

癌間質が豊富な固形癌モデルでの治療効果評価を実施し,期待以上の治療効果を得るなど,計画通りに進捗しているため。

Strategy for Future Research Activity

新たな治療オプションとしても併用療法の治療効果の検証を継続する予定である。

Report

(4 results)
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(13 results)

All 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 12 results,  Open Access: 10 results) Book (1 results)

  • [Journal Article] Preclinical evaluation of podoplanin-targeted al-pha-radioimmunotherapy with the novel antibody NZ-16 for malignant mesothelioma2021

    • Author(s)
      Asano T, Suzuki H, Kaneko MK, Kato Y.
    • Journal Title

      Cells.

      Volume: 10 Pages: 2503-2503

    • DOI

      10.3390/cells10102503

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative Radionuclide Imaging Analysis of Enhanced Drug Delivery Induced by Photoimmunotherapy2021

    • Author(s)
      Aung Winn、Tsuji Atsushi B.、Sugyo Aya、Fujinaga Masayuki、Zhang Ming-Rong、Higashi Tatsuya
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Pages: 8316-8316

    • DOI

      10.3390/ijms22158316

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Vitro Evaluation of No-carrier-added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons2021

    • Author(s)
      Obata, H., Tsuji, A.B., Sudo, H., Sugyo, A., Minegishi, K., Nagatsu, K., Ogawa, M., Zhang, M.R.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Pages: 4622-4622

    • DOI

      10.3390/ijms22094622

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 64Cu-labeled minibody D2101 visualizes CDH17-positive gastric cancer xenografts with short waiting time2020

    • Author(s)
      Fujiwara Kentaro、Akiba Hiroki、Tsuji Atsushi B.、Sudo Hitomi、Sugyo Aya、Nagatsu Kotaro、Zhang Ming-Rong、Iwanari Hiroko、Kusano-Arai Osamu、Kudo Shota、Kikuchi Chika、Tsumoto Kouhei、Momose Toshimitsu、Hamakubo Takao、Higashi Tatsuya
    • Journal Title

      Nuclear Medicine Communications

      Volume: Publish Ahead of Print Pages: 688-695

    • DOI

      10.1097/mnm.0000000000001203

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Radiolabeled Human Monoclonal Antibody 067-213 has the Potential for Noninvasive Quantification of CD73 Expression2020

    • Author(s)
      Sudo Hitomi、Tsuji Atsushi B.、Sugyo Aya、Kurosawa Gene、Kurosawa Yoshikazu、Alexander David、Tsuda Hiroyuki、Saga Tsuneo、Higashi Tatsuya
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Pages: 2304-2304

    • DOI

      10.3390/ijms21072304

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proof of Concept Study for Increasing Tenascin-C-Targeted Drug Delivery to Tumors Previously Subjected to Therapy: X-Irradiation Increases Tumor Uptake2020

    • Author(s)
      Sugyo Aya、Tsuji Atsushi B.、Sudo Hitomi、Takano Kanako、Kusakabe Moriaki、Higashi Tatsuya
    • Journal Title

      Cancers

      Volume: 12 Pages: 3652-3652

    • DOI

      10.3390/cancers12123652

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-Dose Cisplatin Pre-Treatment Enhances Efficacy of ROBO1-Targeted Radioimmunotherapy2020

    • Author(s)
      Fujiwara Kentaro、Koyama Keitaro、Tsuji Atsushi B.、Iwanari Hiroko、Kusano-Arai Osamu、Higashi Tatsuya、Momose Toshimitsu、Hamakubo Takao
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Pages: 7728-7728

    • DOI

      10.3390/ijms21207728

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Radiotheranostic Agent 64Cu-cyclam-RAFT-c(-RGDfK-)4 for Management of Peritoneal Metastasis in Ovarian Cancer2020

    • Author(s)
      Jin Zhao-Hui、Tsuji Atsushi B.、Degardin Melissa、Sugyo Aya、Obara Satoshi、Wakizaka Hidekatsu、Nagatsu Kotaro、Hu Kuan、Zhang Ming-Rong、Dumy Pascal、Boturyn Didier、Higashi Tatsuya
    • Journal Title

      Clinical Cancer Research

      Volume: 26 Pages: 6230-6241

    • DOI

      10.1158/1078-0432.ccr-20-1205

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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: 23712378-23712378

    • DOI

      10.3892/or.2019.7017

    • Related Report
      2019 Annual Research 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) Pages: 5491-5504

    • DOI

      10.3748/wjg.v24.i48.5491

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Direct comparison of 2?amino[3?11C]isobutyric acid and 2?amino[11C]methyl?isobutyric acid uptake in eight lung cancer xenograft models2018

    • Author(s)
      Sudo Hitomi、Tsuji Atsushi、Sugyo Aya、Okada Maki、Kato Koichi、Zhang Ming?Rong、Saga Tsuneo、Higashi Tatsuya
    • Journal Title

      International Journal of Oncology

      Volume: 53 Pages: 2737-2744

    • DOI

      10.3892/ijo.2018.4596

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy Evaluation of Combination Treatment Using Gemcitabine and Radioimmunotherapy with 90Y-Labeled Fully Human Anti-CD147 Monoclonal Antibody 059-053 in a BxPC-3 Xenograft Mouse Model of Refractory Pancreatic Cancer2018

    • Author(s)
      Sugyo Aya、Tsuji Atsushi、Sudo Hitomi、Koizumi Mitsuru、Ukai Yoshinori、Kurosawa Gene、Kurosawa Yoshikazu、Saga Tsuneo、Higashi Tatsuya
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Pages: 2979-2979

    • DOI

      10.3390/ijms19102979

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Book] Cancer Drug Delivery Systems Based on the Tumor Microenvironment2019

    • Author(s)
      Tsuji, A., Saga, T.
    • Total Pages
      325
    • Publisher
      Springer
    • ISBN
      9784431568780
    • Related Report
      2019 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-12-28  

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