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

EBioMedicine

Sanjive Qazi¹  Fatih M. Uckun¹  Dorothea E. Myers¹  Jianjun Cheng² 

[1] Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles (CHLA), Los Angeles, CA 90027, USA;Department of Materials Science and Engineering, University of Illinois at Urbana–Champaign (UIUC), Urbana, IL 61801, USA;

关键词: Leukemia;    Bone marrow transplantation;    Total body irradiation;    Radiation resistance;    Personalized medicine;    Precision medicine;    Cancer;   

DOI  :  10.1016/j.ebiom.2015.04.005

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown