Identification of Small Ligands Targeting Breast Cancer by In Vivo Screening of Peptide Laboratories in Breast Cancer Patients
Abstract
The purpose of this research is to develop methods of generating tumor specific small peptides that will bind to human cancers. The goal is to develop an in vivo serial selection method of tumor-binding peptides from tumor nodules following intravenous administration of peptide phage to tumor-bearing mice. In particular, following IV infusion of naive phage library, phage collected from a surgically harvested tumor were amplified and readministered to the same tumor-bearing animal. This process was repeated twice so that one naive and two enriched phage samples were administered. It was identified that phage could be successfully recovered from a tumor nodule, amplified and readministered to the same organism. The mice tolerated the serial panning procedure with relatively little toxicity. Phage recovered from the final harvested tumor (3rd pan) were sequenced and amino acid consensus sequences were identified. One of the sequences shared a motif with a reported MMP binding peptide. Based on this work, the Food and Drug Administration has approved a phase I human study utilizing the protocol of the preclinical murine model system. In addition, a clinical study, based on this preclinical work, has been funded by the National Cancer Institute and is now open for accrual.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADB286127
Entities
People
- David N Krag
Organizations
- University of Vermont