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Identification of multiple myeloma stem cells and establishment of antibody therapy against them

Research Project

Project/Area Number 21790917
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionOsaka University

Principal Investigator

HOSEN Naoki  Osaka University, 大学院・医学系研究科, 准教授 (10456923)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords多発性骨髄腫 / 腫瘍幹細胞 / 癌幹細胞 / 抗体療法 / 抗体医薬
Research Abstract

CD19^+ cells from peripheral blood or bone marrow (BM) of MM patients were transplanted to NOD/Scid,IL-2Rγnull mice. However, MM disease did not develop in the recipient mice even in the transplants with highly expanded clonotypic CD19^+ B cells. On the other hand, in the SCID-rab model, CD38^<++> MM plasma cells, but not CD19^+ B cells, from MM patients engrafted and generated MM disease in rabbit BM that had been implanted subcutaneously in SCID mice. While CD138- BM cells, in which MM progenitors were reported to exist, generated MM disease in the SCID-rab model, the engrafting cells were CD38^<++>CD138^- plasma cells, not CD19^+ B cells. These results indicate that MM progenitor cells that can initiate and maintain MM disease are present in CD38^<++> plasma cells. We also found that CD48, a cell surface glycoprotein not previously associated with MM, is a promising candidate as a target antigen for antibody therapy against MM. One of the newly generated anti-CD48 mAbs significantly inhibited tumor growth in SCID mice inoculated with MM cells.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (14 results)

All 2010 2009

All Presentation (12 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Presentation] Multiple myeloma progenitor cells exist in CD19^-CD38^<++> plasma cell population2010

    • Author(s)
      保仙直毅
    • Organizer
      第52回米国血液学会
    • Place of Presentation
      オーランド、米国
    • Year and Date
      2010-12-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] Clonogenic myeloma progenitor exists in CD19-CD38^<++> plasma cells2010

    • Author(s)
      保仙直毅、杉山治夫
    • Organizer
      米国血液学会
    • Place of Presentation
      オーランド、米国
    • Year and Date
      2010-12-04
    • Related Report
      2010 Final Research Report
  • [Presentation] MMSC-1 as a novel molecular target for antibody therapy in multiple myeloma2010

    • Author(s)
      保仙直毅、津子、川上学、山上保、村上雅樹、玉置広哉、中尾隆文、藤重夫、中島博子、日野雅之、岡芳弘、杉山治夫
    • Organizer
      日本血液学会
    • Place of Presentation
      横浜
    • Year and Date
      2010-09-26
    • Related Report
      2010 Final Research Report
  • [Presentation] MMSC-1 as a novel molecular target for antibody therapy in multiple myeloma2010

    • Author(s)
      保仙直毅
    • Organizer
      第72回日本血液学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2010-09-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] Clonogenic myeloma progenitor exists in CD19-CD38^<++> plasma cells2010

    • Author(s)
      保仙直毅、岸田諭、松岡由和、市原弘善、青山泰孝、麥谷安津子、川上学、山上保、村上雅樹、玉置広哉、中尾隆文、藤重夫、中島博子、日野雅之、岡芳弘、杉山治夫
    • Organizer
      日本血液学会
    • Place of Presentation
      横浜
    • Year and Date
      2010-09-25
    • Related Report
      2010 Final Research Report
  • [Presentation] Multiple myeloma progenitor cells exist in CD19^-CD38^<++> plasma cell population2010

    • Author(s)
      保仙直毅
    • Organizer
      第72回日本血液学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2010-09-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] 腫瘍幹細胞:B細胞性腫瘍幹細胞からの考察(ランチョンセミナー)2010

    • Author(s)
      保仙直毅
    • Organizer
      日本癌学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Final Research Report
  • [Presentation] 腫瘍幹細胞:B細胞系悪性腫瘍からの考察2010

    • Author(s)
      保仙直毅
    • Organizer
      第69回日本癌学会総会ランチョンセミナー
    • Place of Presentation
      大阪(招待講演)
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification and targeting of multiple myeloma progenitor cells2010

    • Author(s)
      保仙直毅、岸田諭、中田潤、松岡由和、杉山治夫
    • Organizer
      幹細胞シンポジウム
    • Place of Presentation
      淡路島
    • Year and Date
      2010-05-13
    • Related Report
      2010 Final Research Report
  • [Presentation] MMSC-1 is a novel target molecule for antibody therapy against both multiple myeloma progenitor cells and mature myeloma plasma cells2009

    • Author(s)
      保仙直毅
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      スイス
    • Year and Date
      2009-09-16
    • Related Report
      2010 Final Research Report
  • [Presentation] MMSC-1 is a novel target molecule for antibody therapy against both multiple myeloma progenitor cells and mature myeloma plasma cells2009

    • Author(s)
      保仙直毅
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      ジュネーブ(スイス)
    • Year and Date
      2009-09-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] 多発性骨髄腫に対する抗体療法のための新規標的抗原2009

    • Author(s)
      保仙直毅、水谷陽介、小林丈二、岸田諭、岡芳弘、川瀬一郎、杉山治夫
    • Organizer
      日本造血器腫瘍免疫療法研究会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-08-28
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 形質細胞の腫瘍性増殖をきたす疾患の治療薬2010

    • Inventor(s)
      保仙直毅
    • Industrial Property Rights Holder
      国立大学法人大阪大学 杉山治夫
    • Filing Date
      2010-04-09
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] THERAPEUTIC AGENT FOR DISEASES IN WHICH NEOPLASTIC PROLIFERATION OF PLASMA CELLS OCCURS2010

    • Inventor(s)
      保仙直毅, 杉山治夫
    • Industrial Property Rights Holder
      大阪大学
    • Filing Date
      2010-04-10
    • Related Report
      2010 Annual Research Report
    • Overseas

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Published: 2009-04-01   Modified: 2016-04-21  

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