2014 Fiscal Year Final Research Report
Targeting myeloma progenitors by ex vivo-expanded gamma delta T cell
| Project/Area Number |
25860789
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
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| Research Collaborator |
NAKAMURA Shingen
HARADA Takeshi
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | 多発性骨髄腫 / γδT細胞 / lenalidomide |
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| Outline of Final Research Achievements |
Lenalidomide (Len) was able to expand γδ T cells more robustly in combination with HMB-PP than Zol from PBMCs from the majority of normal donors. However, Len alone did not show any significant effects on γδ T cell expansion and activation, suggesting a costimulatory role of Len on Zol or HMB-PP-primed γδ T cells. The surface expression of LFA-1, NKG2D, DNAM-1 and TRAIL were up-regulated in the expanded γδ T cells. Len in combination with either Zol or HMB-PP enhanced intracellular IFN-γ along with the surface NKG2D, suggesting robust induction of Th1-like γδ T cells by Len. Importantly, γδ T cells expanded with the combinatory treatments with Len and Zol or HMB-PP exerted potent cytotoxic activity against multiple myeloma (MM) cells. Interestingly, the expanded γδ T cells markedly suppressed the colony formation in RPMI8226 and KMS-11 cells, and decreased in size their side populations, suggesting targeting a drug-resistant clonogenic MM cells.
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| Free Research Field |
血液内科
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