2023 Fiscal Year Final Research Report
development of combined immunotherapy targeting ero1 in triple negative breast cancer
| Project/Area Number |
20K08935
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
Kutomi Goro 札幌医科大学, 医学部, 講師 (10404625)
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| Co-Investigator(Kenkyū-buntansha) |
島 宏彰 札幌医科大学, 医学部, 講師 (00404616)
和田 朝香 札幌医科大学, 医学部, 研究員 (10830151)
鳥越 俊彦 札幌医科大学, 医学部, 教授 (20301400)
廣橋 良彦 札幌医科大学, 医学部, 准教授 (30516901)
竹政 伊知朗 札幌医科大学, 医学部, 教授 (50379252)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 腫瘍免疫 / 乳癌 |
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| Outline of Final Research Achievements |
In this study, we performed vitro and vivo experiments with the main species of molecules whose relevance has been suggested in the past in treatment-resistant triple-negative breast cancer. First, we performed functional analysis of the ERO1-Lα inhibitor derivative itself, and confirmed that inhibition itself actually caused events similar to knockdown. Next, we conducted experiments in mice by blocking ERO1-Lα using an ERO1-Lα inhibitor derivative and simultaneously using anti-PD-L1 and anti-VEGF antibodies as combined immunotherapy with a triple blocking target, and the results showed that the ERO1-Lα inhibitor derivative, anti-PD-L1 and anti-VEGF antibodies were effective in blocking ERO1-Lα. The results showed that the combined use of ERO1-Lα inhibitor derivatives, anti-PD-L1 and anti-VEGF antibodies showed anti-tumor effects, which are very important research results as the first step in the development of immunocompound therapy.
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| Free Research Field |
乳癌腫瘍免疫治療
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、治療法の限られているトリプルネガティブ（TN）乳癌の新たな治療標的の発見という点で、次世代のTN乳癌治療の発展に貢献できると考え計画した。乳癌細胞におけるERO1-Lαの発現と悪性度について研究を進められてきた。そのERO1-Lαの発現を阻害することにより癌細胞特異的であり、ERO1-Lα誘導体阻害剤を用いて、さらに抗VEGF抗体と抗PD-L1抗体と加えることによって、標的をトリプルにすることで強力な免疫複合治療を開発できるという可能性が強く示唆された。
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