| Project/Area Number |
26830109
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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 |
Tumor therapeutics
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| Research Institution | Ehime University |
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Principal Investigator |
ASAI HIROAKI 愛媛大学, 医学部附属病院, 講師(病院職員) (00726838)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 細胞免疫療法 / 白血病性幹細胞 / WT1 |
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| Outline of Final Research Achievements |
Suppression of leukemia stem cells (LSC) is reasonably necessary to cure the leukemia. To this end, we are developing a redirected T cell-based adoptive immunotherapy targeting WT1, which LSCs have been shown to overexpress. In this study, we have demonstrated WT1-siTCR/CD8+ T cells killed Fucci-labeled leukemia cell lines irrelevantly to the cell-cycle status of target leukemia cells with in vitro time lapse assay, and also demonstrated WT1-siTCR/CD8+ T cells seem be able to kill cell-cycle quiescent LSCs using a xenograft NOG mouse model in vivo. In addition, we found that WT1-siTCR/CD4+ T cells migrated to leukemia sites, subsequently attracted WT1-siTCR/CD8+ T cells via chemotaxis, and augmented cytocidal activity against human leukemia through longer survival and enhanced formation of memory T cells by WT1-siTCR/CD8+ T cells. Collectively, our experimental findings strongly suggest that this strategy would be clinically advantageous for the treatment of human leukemia.
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