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Establishment of near-infrared photoimmunotherapy targeting CD73 using mouse lung cancer model

Research Project

Project/Area Number 21K07189
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionHokkaido University

Principal Investigator

Hatanaka Yutaka  北海道大学, 大学病院, 特任准教授 (30589924)

Co-Investigator(Kenkyū-buntansha) 加藤 達哉  北海道大学, 大学病院, 教授 (20624232)
小川 美香子  北海道大学, 薬学研究院, 教授 (20344351)
畑中 佳奈子  北海道大学, 大学病院, 特任講師 (10399834)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsCD73 / 免疫チェックポイント阻害治療 / 非小細胞肺癌 / CD73/NT5E / 赤外光線免疫療法
Outline of Research at the Start

がん微小環境において、アデノシン産生が亢進するとリンパ球上のA2受容体を介して免疫抑制状態を誘導し,免疫チェックポイント阻害(ICI)療法に対し抵抗性を示すことが知られている。先行研究において,我々は非小細胞肺癌の一部でCD73発現が亢進し,またPD-L1発現と相関することを明らかにした.本研究では、マウス肺癌モデルを用いたCD73を標的とした近赤外光線免疫療法およびICIとの併用療法の確立・検証を行う。

Outline of Final Research Achievements

In the cancer microenvironment, enhanced adenosine production induces immune suppression through the A2 receptor on lymphocytes, leading to resistance to immune checkpoint inhibitor (ICI) therapy. In this study, we established near-infrared light immunotherapy (NIR-PIT) targeting CD73, an enzyme that converts AMP to adenosine, using a mouse lung cancer model. When NIR-PIT with CD73-IR700 complex was performed on syngeneic transplanted mice with CD73-positive mouse lung cancer cell lines, anti-tumor effects were observed. Furthermore, the combination with anti-PD-1 therapy further enhanced its efficacy, demonstrating the effectiveness of this therapy targeting CD73 alone and in combination with ICI therapy by anti-PD-1 in vivo.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果から,アデノシンカスケードにおいて細胞外アデノシンの生成の律速ステップであるCD73を標的としたNIR-PIT単独療法および抗PD-1抗体を用いた免疫チェックポイント阻害(ICI)療法を上乗せした併用療法の有効性がマウス肺癌細胞株移植腫瘍モデルにおいて示された.NIR-PITは新規治療技術であり,またCD73は新規がん免疫関連標的分子であることから,新たな治療選択肢の提供に向けた臨床開発が期待される.

Report

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

    (9 results)

All 2024 2023 2022 2021

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 5 results)

  • [Journal Article] Exhaustion, rather than lack of infiltration and persistence, of CAR-T cells hampers the efficacy of CAR-T therapy in an orthotopic PDAC xenograft model2024

    • Author(s)
      Yuta Takeuchi, Yizheng Wang, Katsunori Sasaki, Osamu Sato, Takahiro Tsuchikawa, Linan Wang, Yasunori Amaishi, Sachiko Okamoto, Junichi Mineno, Yoshifumi Hirokawa, Kanako C Hatanaka, Yutaka Hatanaka, Takuma Kato, Hiroshi Shiku, Satoshi Hirano
    • Journal Title

      Biomed Pharmacoher

      Volume: 170 Pages: 116052-116052

    • DOI

      10.1016/j.biopha.2023.116052

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Polymorphisms of the PD‐L1 gene 3′‐untranslated region are associated with the expression of PD‐L1 in non‐small cell lung cancer2023

    • Author(s)
      Ohhara Yoshihito、Tomaru Utano、Kinoshita Ichiro、Hatanaka Kanako C.、Noguchi Takuro、Hatanaka Yutaka、Amono Toraji、Matsuno Yoshihiro、Dosaka‐Akita Hirotoshi
    • Journal Title

      Genes, Chromosomes and Cancer

      Volume: 63 Issue: 1

    • DOI

      10.1002/gcc.23216

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Programmed death ligand 1-positive immune cells in primary tumor or metastatic axillary lymph nodes can predict prognosis of triple-negative breast cancer even when present at < 1% in the tumor region2023

    • Author(s)
      Tomioka Nobumoto、Hatanaka Kanako C.、Okuyama Dai、Watanabe Ken-ichi、Yamamoto Mitsugu、Maeda Hideki、Tachikawa Hanae、Kuwahara Sayuri、Shimizu Ai、Suzuki Hiroaki、Hatanaka Yutaka、Takahashi Masato
    • Journal Title

      Breast Cancer

      Volume: 30 Issue: 4 Pages: 689-690

    • DOI

      10.1007/s12282-023-01454-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Budget impact analysis of next-generation sequencing versus sequential single-gene testing in Japanese patients with advanced non-small-cell lung cancer2023

    • Author(s)
      Matsuda Hiroyuki、Ogawa Toru、Sadatsuki Yasunari、Tsujino Toshiaki、Wada Shingo、Kim Seok-Won、Hatanaka Yutaka
    • Journal Title

      Respiratory Investigation

      Volume: 61 Issue: 1 Pages: 61-73

    • DOI

      10.1016/j.resinv.2022.10.002

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Guidelines for Handling of Cytological Specimens in Cancer Genomic Medicine2023

    • Author(s)
      Morii Eiichi、Hatanaka Yutaka、Motoi Noriko、Kawahara Akihiko、Hamakawa Shinji、Kuwata Takeshi、Nagatomo Tadasuke、Oda Yoshinao、Okamoto Aikou、Tanaka Ryota、Iyoda Akira、Ichiro Maeda、Matsuo Yukiko、Nakamura Nobuyuki、Nakai Tokiko、Fukuhara Mei、Tokita Kazuya、Yamaguchi Tomohiko、Takenaka Masataka、et al.
    • Journal Title

      Pathobiology

      Volume: Online ahead of print. Issue: 5 Pages: 1-23

    • DOI

      10.1159/000528346

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Notch pathway regulates osimertinib drug-tolerant persistence in EGFR-mutated non-small-cell lung cancer2022

    • Author(s)
      Takahashi Hirofumi、Sakakibara‐Konishi Jun、Furuta Megumi、Shoji Tetsuaki、Tsuji Kosuke、Morinaga Daisuke、Kikuchi Eiki、Kikuchi Junko、Noguchi Takuro、Hatanaka Kanako C.、Hatanaka Yutaka、Shinagawa Naofumi、Konno Satoshi
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 4 Pages: 1635-1650

    • DOI

      10.1111/cas.15674

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of Novel Diagnostic Markers for Malignant Pleural Mesothelioma Using a Reverse Translational Approach Based on a Rare Synchronous Tumor2022

    • Author(s)
      Naka Tomoaki、Hatanaka Yutaka、Tabata Yukiko、Takasawa Akira、Akiyama Hideo、Hida Yasuhiro、Okada Hiromi、Hatanaka Kanako C.、Mitsuhashi Tomoko、Kushitani Kei、Amatya Vishwa Jeet、Takeshima Yukio、Inai Kouki、Kaga Kichizo、Matsuno Yoshihiro
    • Journal Title

      Diagnostics

      Volume: 12 Issue: 2 Pages: 316-316

    • DOI

      10.3390/diagnostics12020316

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cyclin-dependent kinase 4 upregulation mediates acquired resistance of dabrafenib plus trametinib in BRAF V600E-mutated lung cancer2021

    • Author(s)
      Hirai Noriko、Hatanaka Yutaka、Hatanaka Kanako C.、Uno Yuji、Chiba Shin-Ichi、Umekage Yasuhiro、Minami Yoshinori、Okumura Shunsuke、Ohsaki Yoshinobu、Sasaki Takaaki
    • Journal Title

      Translational Lung Cancer Research

      Volume: 10 Issue: 9 Pages: 3737-3744

    • DOI

      10.21037/tlcr-21-415

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biglycan, tumor endothelial cell secreting proteoglycan, as possible biomarker for lung cancer2021

    • Author(s)
      Morimoto Hirofumi、Hida Yasuhiro、Maishi Nako、Nishihara Hiroshi、Hatanaka Yutaka、Li Cong、Matsuno Yoshihiro、Nakamura Toru、Hirano Satoshi、Hida Kyoko
    • Journal Title

      Thoracic Cancer

      Volume: - Issue: 9 Pages: 1-11

    • DOI

      10.1111/1759-7714.13907

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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