Liposomal Nanoparticles of a Spleen Tyrosine Kinase P-Site Inhibitor Amplify the Potency of Low Dose Total Body Irradiation Against Aggressive B-Precursor Leukemia and Yield Superior Survival Outcomes in Mice
Year: 2015
Type: article
Abstract: This study was designed to improve the efficacy of radiation therapy against radiation-resistant leukemia. We report that the potency of low dose radiation therapy against B-precursor acute lymphoblastic leukemia (BPL) can be markedly enhanced by combining radiation with a liposomal nanoparticle (LNP) formulation of the SYK-P-site inhibitor C61 ("C61-LNP"). C61-LNP plus low dose total body irradiation (TBI) was substantially more effective than TBI alone or C61-LNP alone in improving the event-free survival outcome NOD/SCID mice challenged with an otherwise invariably fatal dose of human ALL xenograft cells derived from relapsed BPL patients. C61-LNP plus low dose TBI also yielded progression-free survival, tumor-free survival and overall survival outcomes in CD22ΔE12 × BCR-ABL double transgenic mice with advanced stage, radiation-resistant BPL with lymphomatous features that were significantly superior to those of mice treated with TBI alone or C61-LNP alone.
Source: EBioMedicine
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,780
Awards: Amplifying Radiation Potency Against Leukemic Stem Cells, Developing Clinically Applicable, Cancer-Targeting Polymeric Nanoconjugates, Targeting SYK Tyrosine Kinase to Overcome Radiation Resistance in ALL, G7651978077, Targeting SYK Kinase in B-Lineage ALL with CD19-Specific C-61 Nanoparticles, University of Southern California Norris Comprehensive Cancer Center Support Grant (CCSG)
OpenAlex ID: W2136816306