2023 Fiscal Year Final Research Report
Development of novel diagnostic and therapeutic approaches to cancer by analyzing specific features of the immunoglobulin superfamily of molecules.
| Project/Area Number |
20H03525
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
伊東 剛 東京大学, 医科学研究所, 助教 (20733075)
松原 大祐 筑波大学, 医学医療系, 教授 (80415554)
冨谷 智明 埼玉医科大学, 医学部, 教授 (90227637)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 免疫グロブリンスーパーファミリータンパク質 / 肺がん / がん浸潤・転移 / 薬剤耐性 / 免疫チェックポイント |
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| Outline of Final Research Achievements |
Immunoglobulin superfamily molecules (IgSF) were analyzed for their interaction and potential activity in cancer diagnosis and treatment. Firstly, CADM1v8/9 is specifically expressed in testis and small cell lung cancer (SCLC). Thus, antibodies against the fragments of CADM1v8/9 and their glycosylated products were generated and ELISA systems to detect the CADM1v8/9 in sera from SCLC patients was established with high specificity and sensitivity for diagnosis of SCLC. Then, homophilic interaction of CADM1 in SCLC and endothelial cells was demonstrated to be important for its liver metastasis in mice. Moreover, Based on a comprehensive analysis of molecular interactions between approximately 400 molecules of IgSF, VSIG4 and SIGLEC7 were identified as novel candidates for immune checkpoint molecules. Inhibition of the interaction by antibodies against VSIG4 or SIGLEC7 then enhanced the cytotoxic activity of NK cells in vitro. Based on this finding, a patent was filed in 2024.
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| Free Research Field |
ライフサイエンス
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| Academic Significance and Societal Importance of the Research Achievements |
小細胞肺がん(SCLC)は国内年間死亡数1.1万人を超える難治がんで、新規診断、治療法の開発が強く望まれる。本課題で確立したSCLC患者血清による診断系は現行のProGRP, NSEに匹敵し、予後予測が可能な点で優れ、実用化、並びに抗体薬物複合体による治療開発が期待される。また、その悪性、難治性の基盤となる臓器転移を阻止する分子経路の同定は、抗体薬を含む将来の転移抑制医薬品開発につながると期待される。がん免疫療法の中心である免疫チェックポイント阻害剤(ICI)はさらなる新規開発が望まれ、NK細胞を標的とする新規ICIとしてのVSIG4-SIGLEC7阻害は独自性が高く有望で、特許出願した。
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