Identification and display of CRLF2 ligands for targeted nanoparticle delivery to acute lymphoblastic leukemia.

This is the final report for the Sandia Excellence in Engineering Fellowship awarded through the School of Engineering at the University of New Mexico for the 2011-2012 academic year. Acute Lymphoblastic Leukemia (ALL) is the leading cause of cancer death in children. Almost 80% of the children diagnosed with ALL survive, but in order to reach that point, they must undergo intense regimens of systemic chemotherapy with shortand longterm side effects. Moreover, a significant percentage of cases (~30%) show high-risk features that result in relapse or failure to respond to treatment and account for most deaths. The long term goal of this project is to produce nanoparticles based on virus-like particles (VLPs) of the bacteriophage MS2 that specifically target ALL cells for delivery of cytotoxins. By taking advantage of the overexpression in high-risk pediatric ALL of the thymic stromal lymphopoietin (TSLP) receptor, CRLF2, it is possible to identify a peptide ligands specific for the receptor. We recently developed a peptide display and affinity selection system based on MS2 VLPs, thus integrating the targeting ligand identification and drug delivery functions into a single particle. This report summarizes work accomplished toward this goal.