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The targeting effect of Hm2E8b-NCTD-liposomes on B-lineage leukaemia stem cells is associated with the HLF-SLUG axis.
Journal of Drug Targeting 2018 January
To identify an agent with specific activity against B-lineage leukaemia stem cells (B-LSCs), we generated norcantharidin (NCTD)-encapsulated liposomes modified with a novel humanised anti-human CD19 monoclonal antibody, Hm2E8b (Hm2E8b-NCTD-liposomes). These liposomes were specially designed to recognise and kill B-LSCs in vitro, and to decrease non-specific cytotoxicity to untargeted cells. Hm2E8b-NCTD-liposomes selectively ablated B-LSCs through targeting hepatic leukaemia factor (HLF), which is implicated in haematopoietic stem cell regulation and is overexpressed in LSCs. Hm2E8b-NCTD-liposomes decreased HLF protein levels and induced apoptosis in the HAL-01 cell line harbouring the oncoprotein E2A-HLF. This resulted in modulation of the expression of several molecules that govern survival pathways, including HLF, SLUG, NFIL3 and C-Myc, thereby causing the induction of p53 and the mitochondrial caspase cascade. Therefore, the potent in vitro effect of Hm2E8b-NCTD-liposomes on B-LSC activity and survival pathways have the potential to be exploited clinically with appropriate drug combinations.
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