2019 Fiscal Year Final Research Report
Basic study for HBV clearance using cytokines induced by nucleotide analogues
| Project/Area Number |
17K09448
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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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| Research Field |
Gastroenterology
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| Research Institution | International University of Health and Welfare (2018-2019)
National Center for Global Health and Medicine (2017) |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | B型肝炎 / サイトカイン / 免疫賦活 / 核酸アナログ製剤 |
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| Outline of Final Research Achievements |
We found that adefovir (ADV) or tenofovir (TDF) ①induced IFN-lambda3, and ②inhibited interleukin (IL)-10 and induced IL-12, all of which immunologically lead toward hepatitis B virus (HBV) elimination. Combination of ADV or TDF with IFN-alpha showed additional and synergistic effects on those cytokines production. A mechanistic analysis revealed that ADV or TDF inhibited signals that enhanced in tumor cells. We also found several powerful inducers by screening.
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| Free Research Field |
ウイルス性肝炎
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究にて、現在使用されている核酸アナログ製剤のうちADV・TDFには、B型肝炎ウイルス(HBV)排除に有利な免疫状態を誘導するという追加効果があることが判明した。さらに、強力にIFN-lambda3を誘導する候補薬剤も見出した。また、ADV・TDFは肝発癌抑制効果があることも見出したことから、これらを利用したHBV排除、発がん抑制に関する新たな治療戦略が構築されると考えられる。
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