| Project/Area Number |
16H05288
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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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| Research Field |
Gastroenterology
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| Research Institution | Nagoya City University |
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Principal Investigator |
TANAKA Yasuhito 名古屋市立大学, 大学院医学研究科, 教授 (90336694)
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| Co-Investigator(Kenkyū-buntansha) |
岸 裕幸 富山大学, 大学院医学薬学研究部(医学), 教授 (60186210)
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| Research Collaborator |
ISOGAWA masanori
SATO yusuke
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | HBV / B細胞応答 / 抗ウイルス療法 / 新規免疫治療法 / siRNA / MEND / 新規免疫療法 |
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| Outline of Final Research Achievements |
Persistent infection with hepatitis B virus (HBV) causes cirrhosis・hepatocellular carcinoma as well as HBV reactivation, and its termination is urgently needed. Here, we attempted the production and optimization of humanized anti-CD40 antibody that possesses an anti-virus effect. We first evaluated the impact of CD40 activation on HBV-specific T cell receptor transgenic CD8+ T cells that were adoptively transferred into HBV transgenic mice. We found that treatment of HBV transgenic mice with CD40 antibody during the early phase of T cell responses restored functionally of HBV-specific CD8+ T cells and reduced HBV-mRNA expression levels, while the same treatment during the late phase had no impact on these parameters. We also established an ELISPOT assay system that enables us to analyze HBsAg-specific B cell responses in the human peripheral blood.
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| Academic Significance and Societal Importance of the Research Achievements |
現在、HBV持続感染を治癒する有効な治療法はなく、HBV持続感染患者への精神的・経済的な負担は計り知れない。HBVの排除には宿主免疫応答の活性化が必須とされているが、最適なアプローチは全く明らかにされていない。本研究成果から、CD40抗体の投与による免疫賦活効果はHBV特異的CD8+T細胞の分化段階に依存することが明らかになった。さらに、本研究で構築したHBsAg特異的B細胞応答の解析システムにより、CD40抗体などの免疫賦活がB細胞応答に及ぼす影響をより正確に評価できるようになった。これらの結果はHBVに対する免疫治療開発を促進し、HBV持続感染による社会的負担の軽減につながると考えられる。
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