Identification of multiple myeloma stem cells and establishment of antibody therapy against them
Project/Area Number |
21790917
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Single-year Grants |
Research Field |
Hematology
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Research Institution | Osaka 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.
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Report
(3 results)
Research Products
(14 results)