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Role of CD26 molecule in the infection of MERS(Middle East respiratory syndrome) virus and development of new therapy

Research Project

Project/Area Number 26670486
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Infectious disease medicine
Research InstitutionJuntendo University

Principal Investigator

MORIMOTO CHIKAO  順天堂大学, 医学(系)研究科(研究院), 客員教授 (30119028)

Co-Investigator(Kenkyū-buntansha) IWATA Satoshi  順天堂大学, 医学部, 非常勤講師 (00396871)
OHNUMA Kei  順天堂大学, 医学部, 准教授 (10396872)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsMERS感染症 / コロナウイルス / CD26/DPPⅣ / 重症呼吸器感染症 / ヒト化CD26抗体 / CD26単クローン抗体 / アポトーシス / エピトープ / (1) MERS感染症 / トランスジェニックマウス / ① MERS感染症 / ② コロナウイルス / CD26 / ④ 重症呼吸器感染症 / ⑤ ヒト化CD26抗体 / ⑦ CD26単クローン抗体
Outline of Final Research Achievements

We identified the domains of CD26 involved in the binding of Middle East respiratory syndrome coronavirus using distinct clones of anti-CD26 monoclonal antibodies (MAbs). One clone, named 2F9, almost completely inhibited viral entry. The humanized anti-CD26 MAb also significantly inhibited infection. These findings indicate that both 2F9 and humanized Mab are potential therapeutic agents for MERS infection.
MERS infects human bronchial epithelial Calu-3 cells as well as CD26 Jurkat T lymphocyte cells. Unlike severe acute respiratory syndrome (SARS)-CoV, which exclusively infects and releases through the apical route, this virus can do so through either side of polarized Calu-3 cells. Infection results in profound apoptosis irrespective of its production of titers that are lower than those of SARS-CoV. Together, our results provide new insights into the dissemination and pathogenesis of MERS-CoV and may cause in immune defects since it infected in human CD26 T cells.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (30 results)

All 2015 2014

All Journal Article (16 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 16 results,  Open Access: 16 results,  Acknowledgement Compliant: 4 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] DPP4 in anti-tumor immunity: going beyond the enzyme.2015

    • Author(s)
      Ohnuma K, Hatano R, Morimoto C.
    • Journal Title

      Nat Immunol.

      Volume: 16 Issue: 8 Pages: 791-2

    • DOI

      10.1038/ni.3210

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of two commercial ELISAs against an in-house ELISA for measuring soluble CD26 in human serum2015

    • Author(s)
      Ohnuma K, Saito T, Hatano R, Hosono O, Iwata S, Dang NH, Ninomiya H, Morimoto C
    • Journal Title

      J Clin Lab Anal

      Volume: Mar29 Pages: 106-111

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Modulation of immunological responses and amelioration of collagen-induced arthritis by the novel roxithromycin derivative 5-I.2015

    • Author(s)
      Otsuki N, Iwata S, Yamada T, Hosono O, Dang NH, Hatano R, Ohnuma K, Morimoto C.
    • Journal Title

      Mod Rheumatol.

      Volume: 25 Issue: 4 Pages: 562-70

    • DOI

      10.3109/14397595.2014.983262

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of pulmonary GVHD by IL-26+CD4 T lymphocytes through CD26/caveolin-1 interaction2015

    • Author(s)
      Ohnuma K, Hatano R, Aune TM, Otsuka H, Iwata S, Dang NH, Yamada T, Morimoto C
    • Journal Title

      J Immunol.

      Volume: 194 Pages: 3697-3712

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] CD26-mediated induction ofEGR2 and IL-10 as potential regulatory mechanism for CD26 costimulatory pathway2015

    • Author(s)
      Hatano R, Ohnuma K, Otsuka H, Komiya E, Taki I, Iwata S, Dang NH, Okumura K, Morimoto C
    • Journal Title

      J Immunol

      Volume: 16 Pages: 791-792

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The Role of Cas-L/NEDD9 as a Regulator of Collagen-induced Arthritis in a Murine Model2015

    • Author(s)
      Tomoki Katayose, Satoshi Iwata, Naoki Oyaizu, Osamu Hosono, Taketo Yamada, Nam H Dang, Ryo Hatano, Hirotoshi Tanaka, Kei Ohnuma, Chikao Morimoto
    • Journal Title

      Biochem Bilphys Res Commun

      Volume: 印刷中 Issue: 4 Pages: 1069-75

    • DOI

      10.1016/j.bbrc.2015.03.156

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Comparison of Two Commercial ELISAs against an In-House ELISA for Measuring Soluble CD26 in Human Serum.2015

    • Author(s)
      Ohnuma K, Saito T, Hatano R, Hosono O, Iwata S, Dang NH, Ninomiya H, Morimoto C.
    • Journal Title

      J Clin Lab Anal.

      Volume: Vol 29 Issue: 2 Pages: 106-11

    • DOI

      10.1002/jcla.21736

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD26-mediated induction of EGR2 and IL-10 as potential regulatory mechanism for CD26 costimulatory pathway.2015

    • Author(s)
      Hatano R, Ohnuma K, Otsuka H, Komiya E, Taki I, Iwata S, Dang NH, Okumura K, Morimoto C.
    • Journal Title

      J Immunol.

      Volume: Vol 194 Issue: 3 Pages: 960-72

    • DOI

      10.4049/jimmunol.1402143

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of pulmonary GVHD by IL-26+CD4 T lymphocytes through CD26/caveolin-1 interaction2015

    • Author(s)
      Ohnuma K, Hatano R, Aune TM, Otsuka H, Iwata S, Dang NH, Yamada T, Morimoto C
    • Journal Title

      J.Immunol

      Volume: 194(8) Pages: 3697-712

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD9 Negatively Regulates CD26 Expression and Inhibits CD26-Mediated Enhancement of Invasive Potential of Malignant Mesothelioma cells2014

    • Author(s)
      Okamoto T, Iwata S, Yamazaki H, Hatano R, Komiya E, Dang NH, Ohnuma K, Morimoto C.
    • Journal Title

      PLoS One

      Volume: 9

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of monoclonal anti-human CD26 antibodies suitable for immunostaining of formalin- fixed tissue2014

    • Author(s)
      Hatano R, Yamada T, Matsuoka S, Iwata S, Yamazaki H, Komiya E, Okamoto T, Dang NH, Ohnuma K, Morimoto C
    • Journal Title

      Diagn Pathol

      Volume: 9 Issue: 1 Pages: 30-30

    • DOI

      10.1186/1746-1596-9-30

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Grassypeptolides as natural inhibitors of dipeptidyl peptidase 8 and T-cell activation.2014

    • Author(s)
      Kwan JC, Liu Y, Ratnayake R, Hatano R, Kuribara A, Morimoto C, Ohnuma K, Paul VJ, Ye T, Luesch H.
    • Journal Title

      Chembiochem.

      Volume: Vol 15 Issue: 6 Pages: 799-804

    • DOI

      10.1002/cbic.201300762

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma.2014

    • Author(s)
      Yamamoto J, Ohnuma K, Hatano R, Okamoto T, Komiya E, Yamazaki H, Iwata S, Dang NH, Aoe K, Kishimoto T, Yamada T, Morimoto C.
    • Journal Title

      Br J Cancer.

      Volume: Vol 110 Issue: 9 Pages: 2232-45

    • DOI

      10.1038/bjc.2014.151

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD26-mediated regulation of periostin expression contributes to migration and invasion of malignant pleural mesothelioma cells2014

    • Author(s)
      Komiya E, Ohnuma K,Yamazaki H, Hatano R, Iwata S, Okamoto T, Dang NH, Yamada T, Morimoto C
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 4 Pages: 609-15

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blockade of CD26 Signaling Inhibits Human Osteoclast Development2014

    • Author(s)
      Nishida H1, Suzuki H, Madokoro H, Hayashi M, Morimoto C, Sakamoto M, Yamada T
    • Journal Title

      J Bone Miner Res

      Volume: 29 Pages: 609-15

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical significance of soluble CD26 in malignant pleural mesothelioma2014

    • Author(s)
      Fujimoto N, Ohnuma K, Aoe K, Hosono O, Yamada T, Kishimoto T, Morimoto C
    • Journal Title

      PLoS One

      Volume: Dec 19 Pages: 9-12

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] CD26の機能と治療応用2015

    • Author(s)
      森本幾夫
    • Organizer
      中皮腫シンポジウム
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2015-12-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] CD26 Is a Novel Target of Treatment for Tumor Progression and Its Related Bone Disease in Multiple Myelom2015

    • Author(s)
      Nishida H, Morimoto C, Sakamoto M, Yamada T
    • Organizer
      The 57th ASH Annual Meeting and Exposition
    • Place of Presentation
      Orlando, FL, USA
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CD26抗体を基盤とするトランスレーショナルリサーチ2015

    • Author(s)
      森本幾夫
    • Organizer
      第57回日本小児血液・がん学会
    • Place of Presentation
      山梨県山梨市
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] CD26 promotes invasiveness of malignant pleural mesothelioma cell via upregulation of periosti2015

    • Author(s)
      古宮栄利子, 山崎裕人, 山田健人, 森本幾夫
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      愛知県名古屋市
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Antitumor activity of anti-CD26 humanized monoclonal antibody conjugated with triptolide via intranulear transportatio2015

    • Author(s)
      林睦, 間所裕子, 山田幸司, 西田浩子, 坂元亨宇, 森本幾夫, 山田健人
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      愛知県名古屋市
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Clinical significance of soluble CD26 in malignant pleural mesothelioma2015

    • Author(s)
      Fujimoto N, Ohnuma K, Aoe K, Hosono O, Yamada T, Kishimoto T, Morimoto C
    • Organizer
      16th World Conference of Lung Cancer
    • Place of Presentation
      Denver, USA
    • Year and Date
      2015-09-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] First -in- human phase I administration of YS110, a monoclonal antibody directed against the CD26 immunostimulatory molecule in advanced cancer patients2015

    • Author(s)
      Angevin E, Isambert N,Trillet-Lenoir VN,You V, Alxandre J, Zalcman G, Viel P, Farace F, Valleix F, Podoll T, Kuramochi Y, Miyashita I, HosonoO, Dang NH, Ohnuma K, Yamada T, Kaneko Y, Morimoto C.
    • Organizer
      The 2015 ASCO
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2015-05-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] T細胞共刺激分子CD26に基づく全身性エリテマトーデスの病態および疾患活動性の新規バイオマーカーの探索.2015

    • Author(s)
      波多野良, 大沼圭, 石井智徳, 岩田哲史, 奥村康, 関川巖, 森本幾夫
    • Organizer
      第59回日本リウマチ学会学術集会
    • Place of Presentation
      愛知県名古屋市
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] Clinical significance of soluble CD26 in malignant pleural mesotheliom2015

    • Author(s)
      Fujimoto N, Ohnuma K, Aoe K, Hosono O, Yamada T, Kishimoto T, Morimoto C
    • Organizer
      The 103th Annual Meeting of American Association of Cancer Research
    • Place of Presentation
      Philadelphia, USA.
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 胸膜中皮腫における可溶性CD26の臨床有用性に関する検討2014

    • Author(s)
      1)藤本伸一、青江啓介、細野治、山田健人、岸本卓巳、森本幾夫
    • Organizer
      第73回日本癌学会学術集会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] DPP4阻害剤の服用によって誘発される多関節症とそのバイオマーカー2014

    • Author(s)
      1)大沼圭, 斉藤辰彦, 波多野良, 岩田哲史, 鈴木博史, 森本幾夫
    • Organizer
      第58回日本リウマチ学会学術集会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京)
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] L-10産生誘導によるCD26共刺激経路のnegative feedback機構の解析2014

    • Author(s)
      波多野良, 大沼圭, 岩田哲史, 石井智徳, 関川巖, 森本幾夫
    • Organizer
      第58回日本リウマチ学会学術集会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京)
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] CD26抗体と他の抗がん剤とを組み合わせた癌治療用組成物2015

    • Inventor(s)
      山田健人,林睦、山田幸司、森本幾夫、岡本俊博、金子有太郎
    • Industrial Property Rights Holder
      山田健人,林睦、山田幸司、森本幾夫、岡本俊博、金子有太郎
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] 免疫抑制剤2014

    • Inventor(s)
      森本幾夫、大沼圭、波多野良
    • Industrial Property Rights Holder
      順天堂大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-09-29
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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