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

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07189
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Hokkaido 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
• Keywords: CD73 / 免疫チェックポイント阻害治療 / 非小細胞肺癌

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.

Free Research Field

分子診断

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．