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Development of a Tumor-Selective Therapy Using Photo-Responsive Angiogenesis Inhibitors

Research Project

Project/Area Number 20K22824
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0901:Oncology and related fields
Research InstitutionJikei University School of Medicine

Principal Investigator

Nishimura Takashi  東京慈恵会医科大学, 医学部, 助教 (00884785)

Project Period (FY) 2020-09-11 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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)
Keywords光免疫療法 / VEGFR-2 / Minマウス / 大腸癌 / 蛍光内視鏡
Outline of Research at the Start

新たながん治療法である光免疫療法(NIR-PIT)は、光感受性蛍光プローブを結合させた抗体化合物と近赤外光を用いて、がん細胞のみを分子標的特異的に蛍光でイメージングし、イメージングをガイドとした近赤外光の照射によって、標的細胞のみを選択的に細胞死へ誘導する治療法である。
本研究では、がん新生血管内皮細胞発現分子を標的としたNIR-PITにより、マウス大腸炎を背景として自然発症した分子発現に不均一性 (heterogeneity) を持つ大腸腫瘍の分子イメージングと、NIR-PITによる腫瘍の制御を試みる。

Outline of Final Research Achievements

The purpose of this study is to evaluate the efficacy of a newly developed photoimmunotherapy (PIT) targeting tumor endothelial cells in spontaneously developed colorectal cancer in ApcMin/+ mice. The study utilizes a photosensitive antibody compound (DC101-IR700) targeting VEGFR-2, expressed on the endothelial cells. The fluorescence accumulation in the tumor was confirmed via endoscopy following the administration of the compound. Subsequent exposure of the tumor to near-infrared light initiated the PIT process. A significant antitumor effect was observed when compared to untreated controls.
After treatment, pathological examination revealed the disappearance of cancer cells, infiltration of inflammatory cells, and fibrinoid necrosis of the vascular endothelium. These findings confirmed that the antitumor effects were mediated through vascular endothelial injury within the tumor.

Academic Significance and Societal Importance of the Research Achievements

腫瘍内血管内皮のVEGFR-2を標的とする新しい光免疫療法(NIR-PIT)がマウス大腸がんの治療として有効であることを証明した。従来の皮下移植モデルとは違い、自然発がんするマウス大腸がんモデルを用いた実験で効果を証明したため、人へ臨床応用しやすいことが期待される。この治療は正常細胞は傷害しないため従来のがん治療法に比べて副作用が少なく、より腫瘍選択的で効果的な大腸がん治療法の確立に寄与する可能性がある。これにより、患者の生存率の向上、及び生活の質の改善が期待される。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (3 results)

All 2023 2022

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

  • [Journal Article] Photoimmunotechnology as a powerful biological tool for molecular-based elimination of target cells and microbes, including bacteria, fungi and viruses2023

    • Author(s)
      Iwase Tadayuki、Ito Kimihiro、Nishimura Takashi、Miyakawa Kei、Ryo Akihide、Kobayashi Hisataka、Mitsunaga Makoto
    • Journal Title

      Nature Protocols

      Volume: 18 Issue: 11 Pages: 3390-3412

    • DOI

      10.1038/s41596-023-00874-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Near-infrared photoimmunotherapy for colitis-associated colorectal cancer in a mouse model.2023

    • Author(s)
      Takashi Nishimura, Makoto Mitsunaga, Hiroki Saijo, Masayuki Saruta
    • Organizer
      Asian Pacific Digestive Week 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウス潰瘍性大腸炎関連大腸癌に対する近赤外セラノスティクス内視鏡2022

    • Author(s)
      西村 尚、光永 眞人
    • Organizer
      日本癌学会学術総会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2020-09-29   Modified: 2025-01-30  

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