Development of redirected T cell-based adoptive immunotherapy targeting leukemia stem cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 26830109
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Ehime University
• Principal Investigator: ASAI HIROAKI 愛媛大学, 医学部附属病院, 講師(病院職員) (00726838)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 細胞免疫療法 / 白血病性幹細胞 / WT1

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.

Free Research Field

腫瘍治療学・細胞免疫療法