Breast Tumor Specific Peptides: Development of Breast Carcinoma Diagnostic and Therapeutic Agents
Abstract
The focus of our research was to characterize the tumor imaging and therapeutic potentials of novel peptides that bound two breast tumor antigens, the pancarcinoma Thomsen-Friedenreich (T-antigen) and erbB-2 receptor. Peptides that bound T-antigen and the erbB-2 receptor were originally identified from random peptide bacteriophage display libraries. While the T-antigen binding peptide (P30) was not suitable as a radiolabeled tumor-imaging agent, it did possess remarkable anti-tumor cell adhesive properties. The P30 peptide was able to inhibit MDA-MB-435 breast carcinoma cell-cell adhesion up to 74% and tumor cell-endothelial cell adhesion by greater than 50%. The significance of T-antigen-mediated adhesion in breast cancer identifies T-antigen as a valid target for development of new anti-adhesive therapies of cancer metastases. An erbB-2 receptor binding peptide (p6. 1) was also investigated as a potential breast tumor-imaging agent. We demonstrated that the p6.1 peptide selectively bound the erbB-2 receptor as well as the erbB-1 receptor, both of which are upregulated on many breast carcinomas. An analog of the p6.1 peptide, that contained an N-terminal DOTA metal chelate, was synthesized and radiolabeled. The radiolabeled DOTA-p6. 1 conjugate bound erbB-2 positive tumor cells in vitro, but did not bind normal endothelial cells, highlighting its potential as a tumor imaging agent.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2000
- Accession Number
- ADB264579
Entities
People
- Thomas P. Quinn
Organizations
- University of Missouri