Breast Tumor Specific Peptides: Development of Breast Carcinoma Diagnostic and Therapeutic Agents
Final rept. 1 Oct 1997-1 Oct 2000
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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.
- Anatomy and Physiology
- Medicine and Medical Research