Identification of PD-1 blocked responsive genes and functional analysis based on tumor eradication system in vivo.
| Project/Area Number |
17K19593
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology and related fields
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| Research Institution | Kyoto University |
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Principal Investigator |
Chamoto Kenji 京都大学, 医学研究科, 特定准教授 (50447041)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | PD-1 / がん免疫 / CRISPR / 免疫逃避機構 / 抗腫瘍免疫 / 免疫抑制 / バイオマーカー / 免疫学 / 癌 / 遺伝子 |
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| Outline of Final Research Achievements |
PD-1 blockade cancer immunotherapy revolutionized the cancer treatment. However, there are still substantial population unresponsive to the therapy, and to elute the unresponsive mechanism is urgently necessary. Although many researchers try to identify the responsible genes through genome sequencing and/or in vitro screening using patients' samples, these studies are hampered by several reasons. We established a screening system of responsible genes by combining the CRISPR-based cell library derived from mono cell line and the selection system of tumors through anti-tumor immunity in vivo. Using this system, we identified several tumor genes associated with responsiveness to the PD-1 blockade immunotherapy.
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| Academic Significance and Societal Importance of the Research Achievements |
PD-1抗体がん免疫治療はその治療効果が注目され様々ながん腫に適応されているが、その一方で不応答性の患者の多く存在する。PD-1抗体は高価な薬のため医療経済を圧迫する恐れもある。早急にPD-1抗体に対する有効性を判断するバイオマーカーとのその分子のがん治療における意義を解明し、不応答性患者を救済する手段を考案する必要がある。我々はこれまでのスクリーニンスシステムの問題を改善し、新しい遺伝子スクリーニングシステムを開発した。このシステムをマウスモデルに用い、PD-1抗体治療の治療効果を規定する複数の腫瘍由来遺伝子を同定した。これらの結果は、今後の不応答性原因の解明に大きく貢献するものである。
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Report
(3 results)
Research Products
(31 results)
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[Journal Article] VISTA expressed in tumour cells regulates T cell function2018
Author(s)
Mulati Kumuluzi、Hamanishi Junzo、Matsumura Noriomi、Chamoto Kenji、Mise Nathan、Abiko Kaoru、Baba Tsukasa、Yamaguchi Ken、Horikawa Naoki、Murakami Ryusuke、Taki Mana、Budiman Kharma、Zeng Xiang、Hosoe Yuko、Azuma Miyuki、Konishi Ikuo、Mandai Masaki
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Journal Title
British Journal of Cancer
Volume: 120
Issue: 1
Pages: 115-127
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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