Serine and proline-rich ligands enriched via phage-display technology show preferential binding to BCR/ABL expressing cells

Abstract

Despite the use of targeted therapy, chronic myelogenous leukemia (CML) currently remains incurable with drug therapy, with patients requiring life-long treatment. Developing either a vaccine to prevent the disease or another novel drug to specifically target and eradicate the CML cell will require the identification of CML-associated cell-surface markers and molecules that can bind specifically to the cell surface. In an attempt to discover peptides that bind specifically to cells in the early chronic phase of the disease, we used phage-display technology to identify heptapeptides that bind specifically to the surface of BCR/ABL-expressing fibroblasts. An in vitro system using NIH3T3 stably transfected with pGD210 (BCR/ABL) was used as a model for the chronic phase of the disease. The cells were panned using a linear heptapeptide phage library (Ph.D 7.0) in a negative/positive panning strategy with NIH3T3 containing only the plasmid vector as the wild type control. We identified four novel peptides that were enriched through this technique. These peptides contained either multiple proline residues or serine/threonine-proline pairs and showed a confirmed binding preference for BCR/ABL+ fibroblasts. The peptide Y-R-A-P-W-P-P also showed a binding affinity for granulocytes from untreated CML patients. We have identified several novel peptides that can be used in future studies to identify specific CML cell-surface antigens or provide a novel drug-delivery mechanism.