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.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26285772.
- Also identified by DOI 10.1016/j.ebiom.2015.04.005 and PMC identifier 4535154.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Combined Modality Therapy
- Intracellular Signaling Peptides and Proteins
- Liposomes
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
- Protein Kinase Inhibitors
- Protein-Tyrosine Kinases
- Radiation-Sensitizing Agents