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Development of novel molecular-targeted therapy by humanized anti-CD26 monoclonal antibody in refractory osteolytic bone metastasis

Research Project

Project/Area Number 25430157
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor therapeutics
Research InstitutionKeio University

Principal Investigator

NISHIDA HIROKO Nishida  慶應義塾大学, 医学部, 助教 (80317130)

Co-Investigator(Kenkyū-buntansha) YAMADA Taketo  埼玉医科大学, 医学部, 教授 (60230463)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsCD26 / 破骨細胞 / 破骨前駆細胞 / ヒト化抗CD26モノクローナル抗体 / p38MAPK / mi/Mitf / 骨吸収 / 溶骨性骨転移 / モノクローナル抗体 / TRAP / 溶骨性骨腫瘍 / 多発性骨髄腫 / 血管内皮細胞 / p38 MAPK / 血液内科
Outline of Final Research Achievements

CD26 is expressed on normal human osteoclasts (OCs) and is intensely expressed on activated OCs in osteolytic bone tumors. M-CSF and sRANKL induced human OC differentiation in association with CD26 expression on monocyte-macrophage lineage cells. CD26 expression was accompanied by increased phosphorylation of p38 MAPK, which was crucial for early human OC differentiation. Humanized anti-CD26 monoclonal antibody, huCD26mAb, dose-dependently impaired the formation and function of TRAP/CD26 positive multi-nucleated OCs. It was revealed that huCD26mAb inhibited early OC differentiation via the inactivation of MKK3/6, p38 MAPK in the cytoplasm and subsequent dephosphorylation of mi/Mitf in the nucleus of human OC precursor cells, immediately after RANKL bound to RANK. However, it did not directly inhibit mature OCs. Our results suggest that targeting human OC precursor cells with huCD26mAb may have therapeutic potential for the treatment of osteolytic tumors to reduce bone destruction.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (20 results)

All 2015 2014 2013 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Acknowledgement Compliant: 2 results) Presentation (14 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Isolated central nervous system relapse in type II enteropathy-associated T cell lymphoma2015

    • Author(s)
      西田浩子、遠藤聖、波多野まみ、立川伸雄、間嶋絵梨、橋田里妙、堀眞佐男、小原克之
    • Journal Title

      Rinsho Ketsueki

      Volume: 56 Issue: 6 Pages: 692-698

    • DOI

      10.11406/rinketsu.56.692

    • NAID

      130005093090

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Blockade of CD26 Signaling Inhibits Human Osteoclast Development2014

    • Author(s)
      Hiroko Nishida, Hiroshi Suzuki, Hiroko Madokoro, Mutsumi Hayashi, Chikao Morimoto, Michiie Sakamoto, Taketo Yamada
    • Journal Title

      Journal of Bone and Mineral Resarch

      Volume: 29 Issue: 11 Pages: 2439-2455

    • DOI

      10.1002/jbmr.2277

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Optic Nerve Involvement of Waldenstrom's Macroglobulinemia - with Autopsy Findings2014

    • Author(s)
      Hiroko Nishida, Risa Hashida, Mami Hatano, Masao Hori, Katsuyuki Obara
    • Journal Title

      Neurological Sciences

      Volume: 35 Pages: 1299-1302

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nuclear localization of CD26 induced by a humanized monoclonal antibody inhibits tumor cell growth by modulating of POLR2A transcription2013

    • Author(s)
      Yamada K, Hayashi M, Madokoro H, Nishida H, Du W, Ohnuma K, Sakamoto M, Morimoto C, Yamada T
    • Journal Title

      PLoS One

      Volume: 8 Issue: 4 Pages: e62304-e62304

    • DOI

      10.1371/journal.pone.0062304

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Report of 2 cases of Disseminated Invasive Aspergillosis with Myocarditis in Immunocompromised Patients2013

    • Author(s)
      Tetsuhiro Yoshino, Hiroko Nishida, Michihiro Sakauchi, Masanori Nemoto, Mami Hatano, Kazuyuki Koyama, Masao, Hori, Katsuyuki Obara
    • Journal Title

      OJPathology

      Volume: 3 Issue: 04 Pages: 166-169

    • DOI

      10.4236/ojpathology.2013.34030

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] CD26 is a novel target for the treatment of tumor progression and its related osteolytic bone disease.2015

    • Author(s)
      Hiroko Nishida, Hiroshi Suzuki, Hiroko Madokoro, Mutsumi Hayashi, Chikao Morimoto, Michiie Sakamoto, Taketo Yamada
    • Organizer
      57th American Society of Hematology Annual Meeting and Exposition
    • Place of Presentation
      オーランド(アメリカ)
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Blockade of CD26 signaling using humanized antibody reduces myeloma cell growth and its bone disease.2015

    • Author(s)
      Hiroko Nishida, Hiroko Madokoro, Hiroshi Suzuki, Mutsumi Hayashi, Chikao Morimoto, Michiie Sakamoto, Taketo Yamada
    • Organizer
      77th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      石川県立音楽堂・ホテル日航金沢(石川県金沢市)
    • Year and Date
      2015-10-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Optic nerve involvement of Waldenstrom's macroglobulinemia2015

    • Author(s)
      Hiroko Nishida, Risa Hashida, Mami Hatano, Masao Hori, Katsuyuki Obara
    • Organizer
      77th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      石川県立音楽堂・ホテル日航金沢(石川県金沢市)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Antitumor activity of anti-CD26 humanized monoclonal antibody conjugated with triptlide via intranuclear transportation2015

    • Author(s)
      Mustumi Hayashi, Kohji Yamada, Hiroko Nishida, Michiie Sakamoto, Chikao Morimoto, Taketo Yamada
    • Organizer
      74th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 破骨細胞による骨髄腫細胞のCD26発現誘導と細胞増殖・生存の亢進~ヒト化抗CD26抗体療法を目指して2015

    • Author(s)
      西田浩子、間所裕子、林睦、坂本亨宇、山田健人
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-05-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 経腸栄養中に銅欠乏性貧血をきたした一例2015

    • Author(s)
      間嶋絵梨、西田浩子、小原克之
    • Organizer
      第203回日本内科学会茨城地方会
    • Place of Presentation
      茨城県立健康プラザ (茨城県水戸市)
    • Year and Date
      2015-03-14
    • Related Report
      2014 Research-status Report
  • [Presentation] Humanized anti-CD26 monoclonal antibody blocks osteoclast differentiation in multiple myeloma2014

    • Author(s)
      Hiroko Nishida, Hiroshi Suzuki, Hiroko Madokoro, Mutsumi Hayashi, Michiie Sakamoto, Chikao Morimoto, Taketo Yamada
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪国際会議場 (大阪府大阪市)
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] Sustained complete remission in a patient with primary B-cell lymphoma of the caudal equina2014

    • Author(s)
      Hiroko Nishida, Masao Hori, Mami Hatano, Keiji Yamaguchi, Katsuyuki Obara
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪国際会議場 (大阪府大阪市)
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] Targeting CD26 on both osteoclast and tumor cell in osteolytic bone metastasis with humanized anti-CD26 monoclonal antibody.2014

    • Author(s)
      Hiroko Nishida, Chikao Morimoto, Michiie, Sakamoto, Taketo, Yamada
    • Organizer
      第73回日本癌学会学術集会
    • Place of Presentation
      パシフィコ横浜 (神奈川県神奈川市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒト化抗CD26モノクローナル抗体によるヒト破骨細胞分化抑制2014

    • Author(s)
      西田浩子、林 睦、坂元亨宇、山田健人
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場、ANAクラウンプラザホテル広島 (広島県広島市)
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Humanized Anti-CD26 Monoclonal Antibody Inhibits Osteoclast Bone Resorption Activity via Blockade of P38MAPK Signaling in Multiple Myeloma2013

    • Author(s)
      Hiroko Nishida, Hiroshi Suzuki, Hiroko Madokoro, Mutsumi Hayashi, Chikao Morimoto, Michiie Sakamoto, Taketo Yamada
    • Organizer
      55th American Society of Hematology Annual Meeting and Exposition
    • Place of Presentation
      New Orleans Ernest N. Morial Conventin Center
    • Related Report
      2013 Research-status Report
  • [Presentation] Blockade of CD26 Signaling Impairs Human Osteoclast Development2013

    • Author(s)
      Hiroko Nishida, Hiroko Madokoro, Hiroshi Suzuki, Mutsumi Hayashi, Kohji Yamada, Michiie Sakamoto, Chikao Morimoto, Taketo Yamada
    • Organizer
      75th Japanese Society of Hematology
    • Place of Presentation
      ロイトン札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] CD26 Signaling Involves Human Functional Osteoclast Development2013

    • Author(s)
      Taketo Yamada, Hiroko Nishida, Hiroko Madokoro
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] 肝・骨髄浸潤で発症したMyC/IgH陽性び漫性大細胞型B細胞性リンパ腫の一例

    • Author(s)
      橋田里妙、西田浩子、鈴木孝治、堀眞佐男、小原克之
    • Organizer
      第599回日本内科学会関東地方会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Book] 目でみるトレーニング第2集2013

    • Author(s)
      西田浩子
    • Publisher
      医学書院
    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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