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Sci Rep. 2014 Mar 27;4:4480. doi: 10.1038/srep04480.

Identification and characterization of a suite of tumor targeting peptides for non-small cell lung cancer.

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  • 11] Departments of Internal Medicine, University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-8807, USA [2] The Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-8807, USA.
  • 2Department of Thoracic and Head and Neck Medical Oncology University of Texas MD Anderson Cancer Center.
  • 3Departments of Internal Medicine, University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-8807, USA.
  • 41] Departments of Clinical Sciences, University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-8807, USA [2] The Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-8807, USA.
  • 51] Departments of Internal Medicine, University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-8807, USA [2] Departments of Pharmacology, University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-8807, USA [3] The Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-8807, USA [4] The Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-8807, USA.

Abstract

Tumor targeting ligands are emerging components in cancer therapies. Widespread use of targeted therapies and molecular imaging is dependent on increasing the number of high affinity, tumor-specific ligands. Towards this goal, we biopanned three phage-displayed peptide libraries on a series of well-defined human non-small cell lung cancer (NSCLC) cell lines, isolating 11 novel peptides. The peptides show distinct binding profiles across 40 NSCLC cell lines and do not bind normal bronchial epithelial cell lines. Binding of specific peptides correlates with onco-genotypes and activation of particular pathways, such as EGFR signaling, suggesting the peptides may serve as surrogate markers. Multimerization of the peptides results in cell binding affinities between 0.0071-40 nM. The peptides home to tumors in vivo and bind to patient tumor samples. This is the first comprehensive biopanning for isolation of high affinity peptidic ligands for a single cancer type and expands the diversity of NSCLC targeting ligands.

PMID:
24670678
[PubMed - in process]
PMCID:
PMC3967199
Free PMC Article
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