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

doi:10.1039/c4ib00095a

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

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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 language	English (US)
Pages (from-to)	766-780
Number of pages	15
Journal	Integrative Biology (United Kingdom)
Volume	6
Issue number	8
DOIs	https://doi.org/10.1039/c4ib00095a
State	Published - Aug 2014
Externally published	Yes

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Myers, D. E., Yiv, S., Qazi, S., Ma, H., Cely, I., Shahidzadeh, A., Arellano, M., Finestone, E., Gaynon, P. S., Termuhlen, A., Cheng, J., & Uckun, F. M. (2014). CD19-antigen specific nanoscale liposomal formulation of a SYK P-site inhibitor causes apoptotic destruction of human B-precursor leukemia cells. Integrative Biology (United Kingdom), 6(8), 766-780. https://doi.org/10.1039/c4ib00095a

Myers, DE, Yiv, S, Qazi, S, Ma, H, Cely, I, Shahidzadeh, A, Arellano, M, Finestone, E, Gaynon, PS, Termuhlen, A, Cheng, J & Uckun, FM 2014, 'CD19-antigen specific nanoscale liposomal formulation of a SYK P-site inhibitor causes apoptotic destruction of human B-precursor leukemia cells', Integrative Biology (United Kingdom), vol. 6, no. 8, pp. 766-780. https://doi.org/10.1039/c4ib00095a

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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.",

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AU - Ma, Hong

AU - Cely, Ingrid

AU - Shahidzadeh, Anoush

AU - Arellano, Martha

AU - Finestone, Erin

AU - Gaynon, Paul S.

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AU - Uckun, Fatih M.

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AB - 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.

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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

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