Novel ligands for cancer diagnosis: selection of peptide ligands for identification and isolation of B-cell lymphomas.
OBJECTIVE
Lymphoma and leukemia account for nearly 8% of cancer fatalities each year. Present treatments do not differentiate between normal and malignant cells. New reagents that distinguish malignant cells and enable the isolation of these cells from the normal background will enhance the molecular characterization of disease and specificity of treatment.


METHODS
Peptide ligands were selected from a phage-displayed peptide library by biopanning on the B-cell lymphoma line, A20. The isolated peptides were assessed as reagents for identification and isolation of lymphoma cells by flow cytometry and cell capture with magnetic beads.


RESULTS
Two novel peptides and one obtained previously on cardiomyocytes were selected. A20 cells bind phage displaying these peptides 250- to 450-fold over control phage. These phage bind to other bone marrow-derived cancel lines including some macrophage and T cells but do not bind to normal splenocytes. Synthetic constructs of these peptides have binding affinities comparable to B-cell-specific antibodies. Similar to antibodies, these peptides can be used in flow cytometry and magnetic bead capture to distinguish lymphoma cells from normal splenocytes.


CONCLUSIONS
Bone marrow-derived malignant cells express cell surface markers that can be used to distinguish them from normal cells. These results demonstrate the ability to use an unbiased screen to rapidly generate high-affinity peptide ligands for identification and isolation of lymphoma cells.
McGuire
Michael J
MJ
Division of Translational Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, 75390, USA. michael.mcguire@utsouthwestern.edu
Samli
Kausar N
KN
Chang
Ya-Ching
YC
Brown
Kathlynn C
KC
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008024:Ligands; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D032383:Myocytes, Cardiac / Q000378:metabolism; D009928:Organ Specificity; D019151:Peptide Library; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D014408:Biomarkers, Tumor; D008024:Ligands; D019151:Peptide Library; D010455:Peptides