Isolation of lung tumor specific peptides from a random peptide library: generation of diagnostic and cell-targeting reagents.
Discovery of ligands specific to receptor(s) on a surface of a cancer cell could impact clinical issues including functional diagnosis and cell-specific drug delivery. Using a phage display approach, we have isolated 20-mer peptide ligands that bind to 3 different human lung tumor cell lines, NCI-H1299, NCI-H2009, and A549. The panning protocol is unbiased with no selection pressure towards binding a particular cellular receptor. The isolated phage bind to their target cells 24-300 times better than a control phage. Furthermore, the isolated peptides display remarkable cell-specificities and are able to discriminate between normal and cancerous cells as well as different lung tumor cells. The cell-specificities are not coincident with tumor classes indicating that the peptides are able to recognize cell-surface features that are not represented within the classification of tumor type. The isolated peptides are functional outside of the context of the phage and multimerization of the peptide increases its affinity for its given cell type, thus expanding their utility in clinical situations.
Oyama
Tsuksa
T
Center for Biomedical Inventions, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9185, USA.
Sykes
Kathryn F
KF
Samli
Kausar N
KN
Minna
John D
JD
Johnston
Stephen Albert
SA
Brown
Kathlynn C
KC
D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification / Q000175:diagnosis*; D019151:Peptide Library; D010455:Peptides / Q000302:isolation & purification*; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D019151:Peptide Library; D010455:Peptides