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Development of novel immune checkpoint inhibitor therapy by microRNAs

Research Project

Project/Area Number 17K19590
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Tumor biology and related fields
Research InstitutionKyoto University

Principal Investigator

ONO KOH  京都大学, 医学研究科, 准教授 (00359275)

Research Collaborator Izuhara Masayasu  
Rodoriguez Randolph Ruiz  
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
KeywordsPLGAナノ粒子 / 核酸医薬 / がん免疫療法 / マイクロRNA / PD-1 / PD-L1 / CD80 / 免疫チェックポイント
Outline of Final Research Achievements

We have been focused on the functions on microRNAs mainly in cardiovascular field. This time, we have noticed that PD-1, PD-L1, and CD80 are regulated by miR-15a/ 15b/ 16/ 195/ 424/ 497/ 503 family. Therefore, we tried to develop a method to express miR-15a by the use of synthetic double strand RNAs with drug delivery system.

Academic Significance and Societal Importance of the Research Achievements

これまでの研究の中で、生体におけるmicroRNAの働きを明らかにしてきた。さらに効果的なmiRNAの標的となる分子を探索していたところ、免疫チェックポイントタンパク質のPD-1, PD-L1, CD80がmiR-15ファミリー(miR-15a/15b/16/195/424/497/503)によって制御されていることを見いだした。すなわち、miR-15ファミリーを発現させることで、PD-1およびCTLA-4経路の両方を同時に抑制できることになる。本研究においては、miR-15aファミリーをがんの局所に導入して、免疫チェックポイント抑制による新規がん治療法の開発を試みた。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (27 results)

All 2019 2018 2017 2016 Other

All Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 13 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 5 results,  Invited: 6 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] MiR-33a is a therapeutic target in SPG4-related hereditary spastic paraplegia human neurons2019

    • Author(s)
      Nakazeki F、Tsuge I、Horie T、Imamura K、Tsukita K、Hotta A、Baba O、Kuwabara Y、Nishino T、Nakao T、Nishiga M、Nishi H、Nakashima Y、Ide Y、Koyama S、Kimura M、Tsuji S、Naitoh M、Suzuki S、Izumi Y、Kawarai T、Kaji R、Kimura T、Inoue H、Ono K
    • Journal Title

      Clinical Science

      Volume: 133 Issue: 4 Pages: 583-595

    • DOI

      10.1042/cs20180980

    • NAID

      120006937614

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatokine α1-Microglobulin Signaling Exacerbates Inflammation and Disturbs Fibrotic Repair in Mouse Myocardial Infarction2018

    • Author(s)
      Hakuno Daihiko、Kimura Masahiro、Ito Shinji、Satoh Junko、Nakashima Yasuhiro、Horie Takahiro、Kuwabara Yasuhide、Nishiga Masataka、Ide Yuya、Baba Osamu、Nishi Hitoo、Nakao Tetsushi、Nishino Tomohiro、Nakazeki Fumiko、Koyama Satoshi、Hanada Ritsuko、Randolph Ruiz R.、Endo Jin、Kimura Takeshi、Ono Koh
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 1-17

    • DOI

      10.1038/s41598-018-35194-w

    • NAID

      120006645320

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SREBF1/MicroRNA-33b Axis Exhibits Potent Effect on Unstable Atherosclerotic Plaque Formation In Vivo2018

    • Author(s)
      Nishino T、Horie T、Baba O、Sowa N、Hanada R、Kuwabara Y、Nakao T、Nishiga M、Nishi H、Nakashima Y、Nakazeki F、Ide Y、Koyama S、Kimura M、Nagata M、Yoshida K、Takagi Y、Nakamura T、Hasegawa K、Miyamoto S、Kimura T、Ono K.
    • Journal Title

      Arteriosclerosis, Thrombosis, and Vascular Biology

      Volume: 38 Issue: 10 Pages: 2460-2473

    • DOI

      10.1161/atvbaha.118.311409

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating markers of collagen types I, III, and IV in patients with dilated cardiomyopathy: relationships with myocardial collagen expression2018

    • Author(s)
      Nagao Kazuya、Inada Tsukasa、Tamura Akinori、Kajitani Kenji、Shimamura Kiyotaka、Yukawa Hiroshi、Aida Kenji、Sowa Naoya、Nishiga Masataka、Horie Takahiro、Makita Toshinori、Ono Koh、Tanaka Masaru
    • Journal Title

      ESC Heart Failure

      Volume: 5 Issue: 6 Pages: 1044-1051

    • DOI

      10.1002/ehf2.12360

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of periostin ameliorates adipose tissue inflammation and fibrosis in vivo2018

    • Author(s)
      Nakazeki Fumiko、Nishiga Masataka、Horie Takahiro、Nishi Hitoo、Nakashima Yasuhiro、Baba Osamu、Kuwabara Yasuhide、Nishino Tomohiro、Nakao Tetsushi、Ide Yuya、Koyama Satoshi、Kimura Masahiro、Tsuji Shuhei、Sowa Naoya、Yoshida Shigeo、Conway Simon J.、Yanagita Motoko、Kimura Takeshi、Ono Koh
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 8553-8553

    • DOI

      10.1038/s41598-018-27009-9

    • NAID

      120006510274

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MicroRNA-33 regulates the population of peripheral inflammatory Ly6Chigh monocytes through dual pathways.2018

    • Author(s)
      Baba O, Horie T, Hakuno D, Nakashima Y, Nishi H, Kuwabara Y, Nakao T, Nishiga M, Nishino T, Ide Y, Nakazeki F, Koyama S, Kimura M, Hanada R, Kawahara M, Kimura T, and Ono K.
    • Journal Title

      Mol Cell Biol.

      Volume: 38 Issue: 14 Pages: 1-17

    • DOI

      10.1128/mcb.00604-17

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long Non-Coding RNAs as Key Regulators of Cardiovascular Diseases2018

    • Author(s)
      Ono K, Kuwabara Y, Horie T, Kimura T.
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 5 Pages: 1231-1236

    • DOI

      10.1253/circj.CJ-18-0169

    • NAID

      130006725985

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-33 regulates the population of peripheral inflammatory Ly6Chigh monocytes through dual pathways.2018

    • Author(s)
      Baba O, Horie T, Nakao T, Hakuno D, Nakashima Y, Nishi H, Kuwabara Y, Nishiga M, Nishino T, Ide Y, Nakazeki F, Koyama S, Kimura M, Hanada R, Kawahara M, Kimura T, and *Ono K.
    • Journal Title

      Mol Cell Biol.

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long Non-Coding RNAs as Key Regulators of Cardiovascular Diseases.2018

    • Author(s)
      Ono K, Kuwabara Y, Horie T, Kimura T.
    • Journal Title

      Circulation J.

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic Ablation of MicroRNA-33 Attenuates Inflammation and Abdominal Aortic Aneurysm Formation via Several Anti-Inflammatory Pathways.2017

    • Author(s)
      Nakao T, Horie T, Baba O, Nishiga M, Nishino T, Izuhara M, Kuwabara Y, Nishi H, Usami S, Nakazeki F, Ide Y, Koyama S, Kimura M, Sowa N, Ohno S, Aoki H, Hasegawa K, Sakamoto K, Minatoya K, Kimura T, Ono K.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 37 Issue: 11 Pages: 2161-2170

    • DOI

      10.1161/atvbaha.117.309768

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Imbalanced expression of polycistronic miRNA in acute myeloid leukemia.2017

    • Author(s)
      Kotaki R, Higuchi H, Ogiya D, Katahira Y, Kurosaki N, Yukihira N, Ogata J, Yamamoto H, Mohamad Alba S, Azhim A, Kitajima T, Inoue S, Morishita K, Ono K, Koyama-Nasu R, Kotani A.
    • Journal Title

      Int J Hematol.

      Volume: 106 Issue: 6 Pages: 811-819

    • DOI

      10.1007/s12185-017-2314-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prevention of neointimal formation using miRNA-126-containing nanoparticle-conjugated stents in a rabbit model.2017

    • Author(s)
      Izuhara M, Kuwabara Y, Saito N, Yamamoto E, Hakuno D, Nakashima Y, Horie T, Baba O, Nishiga M, Nakao T, Nishino T, Nakazeki F, Ide Y, Kimura M, Kimura T, Ono K.
    • Journal Title

      PLoS One

      Volume: 12(3) Issue: 3 Pages: e0172798-e0172798

    • DOI

      10.1371/journal.pone.0172798

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-33 Controls Adaptive Fibrotic Response in the Remodeling Heart by Preserving Lipid Raft Cholesterol.2016

    • Author(s)
      Nishiga M, Horie T, Kuwabara Y, Nagao K, Baba O, Nakao T, Nishino T, Hakuno D, Nakashima Y, Nishi H, Nakazeki F, Ide Y, Koyama S, Kimura M, Hanada R, Nakamura T, Inada T, Hasegawa K, Conway SJ, Kita T, Kimura T, Ono K.
    • Journal Title

      Circ Res.

      Volume: - Issue: 5 Pages: 835-847

    • DOI

      10.1161/circresaha.116.309528

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] SREBF1/MicroRNA-33b axis exhibits potent effect on unstable atherosclerotic plaque formation in vivo2018

    • Author(s)
      Koh Ono
    • Organizer
      XVIIIth International Symposium on Atherosclerosis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Functions of microRNA-33a/b on inflammation and atherosclerosis2018

    • Author(s)
      Koh Ono
    • Organizer
      China-Japan International Conference on Atherosclerosis 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A Novel Long Intergenic Noncoding RNA, LincRNA-Hy5, Underlies the Heart Development and Guards the Heart from Pressure Overload2018

    • Author(s)
      尾野 亘
    • Organizer
      第50回日本動脈硬化学会総会・学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] マイクロRNAと心血管疾患、代謝性疾患2018

    • Author(s)
      尾野 亘
    • Organizer
      第66回日本心臓病学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] MicroRNA-33の欠損は複数の抗炎症経路を介して大動脈瘤の形成を抑制する2018

    • Author(s)
      尾野 亘
    • Organizer
      第59回日本脈管学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Novel Long Intergenic Noncoding RNA, Lionheart, Guards the Heart from Pressure Overload2018

    • Author(s)
      Kuwabara Y, Horie T, Baba O, Nishiga M, Nakao M, Nishino T, Nakazeki F, Koyama S, Kimura T, Ono K.
    • Organizer
      第82回日本循環器学会
    • Related Report
      2017 Research-status Report
  • [Presentation] MicroRNA-33b promotes atherosclerotic plaque formation in Apoe-/- mice2018

    • Author(s)
      Nishino T, Horie T, Baba O, Kuwabara Y, Hakuno D, Nakashima Y, Nakao T, Nishiga M, Kimura T, Ono K.
    • Organizer
      第82回日本循環器学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Roles of microRNAs in cardiovascular diseases2017

    • Author(s)
      Koh Ono
    • Organizer
      2nd International Symposium for Noncoding RNA Neo-taxonomy In conjunction with Tokyo RNA Club 23rd meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] MicroRNA-33b promotes atherosclerotic plaque formation in Apoe-/- mice.2017

    • Author(s)
      Ono K, Nishino T, Horie T, Kuwabara Y, Nakao T, Nishiga M, Ide Y, Nakazeki F, Koyama S, Kimura M, Kimura T.
    • Organizer
      43rd Naito Conference Noncoding RNA:Biology, Chemistry, & Diseases
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] MicroRNA-33b promotes atherosclerotic plaque formation in Apoe-/- mice.2017

    • Author(s)
      Nishino T, Horie T, Kuwabara Y, Nakao T, Nishiga M, Ide Y, Nakazeki F, Koyama S, Kimura M, Kimura T, Ono K
    • Organizer
      American Heart Association Scientific Sessions 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] 京都大学循環器内科 分子循環器グループ

    • URL

      http://kyoto-u-cardio.jp/kisokenkyu/metabolic/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 心血管疾患分子機構解明グループ

    • URL

      http://kyoto-u-cardio.jp/kisokenkyu/metabolic/

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 遺伝性痙性対麻痺(Hereditary Spastic Paraplegia; HSP)SPG4 に対するmicroRNA-33a抑制療法2018

    • Inventor(s)
      尾野 亘、井上治久、今村恵子、堀江貴裕、中関典子
    • Industrial Property Rights Holder
      尾野 亘、井上治久、今村恵子、堀江貴裕、中関典子
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-119251
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] miR-33bノックインマウスによる非アルコール性脂肪肝炎モデル2018

    • Inventor(s)
      尾野 亘、堀江貴裕、西野共達
    • Industrial Property Rights Holder
      尾野 亘、堀江貴裕、西野共達
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2017 Research-status Report
    • Overseas

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Published: 2017-07-21   Modified: 2021-12-27  

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