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CD19-antigen specific nanoscale liposomal formulation of a SYK P-site inhibitor causes apoptotic destruction of human B-precursor leukemia cells

  • Dorothea E. Myers
  • , Seang Yiv
  • , Sanjive Qazi
  • , Hong Ma
  • , Ingrid Cely
  • , Anoush Shahidzadeh
  • , Martha Arellano
  • , Erin Finestone
  • , Paul S. Gaynon
  • , Amanda Termuhlen
  • , Jianjun Cheng
  • , Fatih M. Uckun

Research output: Contribution to journalArticlepeer-review

Abstract

We report the anti-leukemic potency of a unique biotargeted nanoscale liposomal nanoparticle (LNP) formulation of the spleen tyrosine kinase (SYK) P-site inhibitor C61. C61-loaded LNP were decorated with a murine CD19-specific monoclonal antibody directed against radiation-resistant CD19-receptor positive aggressive B-precursor acute lymphoblastic leukemia (ALL) cells. The biotargeted C61-LNP were more potent than untargeted C61-LNP and consistently caused apoptosis in B-precursor ALL cells. The CD19-directed C61-LNP also destroyed B-precursor ALL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. This unique nanostructural therapeutic modality targeting the SYK-dependent anti-apoptotic blast cell survival machinery shows promise for overcoming the clinical radiochemotherapy resistance of B-precursor ALL cells.

Original languageEnglish (US)
Pages (from-to)766-780
Number of pages15
JournalIntegrative Biology (United Kingdom)
Volume6
Issue number8
DOIs
StatePublished - Aug 2014
Externally publishedYes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

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