2010 Fiscal Year Final Research Report
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 |
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| Research Field |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
HOSEN Naoki Osaka University, 大学院・医学系研究科, 准教授 (10456923)
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| Project Period (FY) |
2009 – 2010
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| Keywords | 多発性骨髄腫 / 腫瘍幹細胞 |
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| 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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