Characterization of Receptors for Peptides Homing to the Vasculature of the Breast Carcinomas by Display Cloning
Abstract
The main problems with current cancer therapies, including those for breast cancer, are that they are only partially effective and highly toxic. The homing peptide technology provides a new targeting strategy that aims at physically concentrating therapeutic agents in tumor tissue by making use of the unique features of tumor vasculature thereby enhancing anti-tumor activity and decreasing side effects. A pentapeptide CREKA, which homes to vasculature of breast tumor in mice, was identified with breast tumor-bearing MMTVPyMT mice by using in vivo screening of phage displayed peptide libraries. The CREKA-displaying phage selectively homes to breast tumors in mice relative to other tumors. The selectivity of the phage homing to breast tumors is about 100-fold relative to non-recombinant phage. Fluorescein-labeled CREKA peptide accumulates in breast tumors, but not normal tissues. Mutating the cysteine (C) residue in CREKA to an alanine preserves the homing activity. Receptor identification experiments indicate that the receptor for the CREKA peptide is related to type IV collagen. Additional screenings of phage peptide libraries against extracellular matrix of breast tumor have been performed, and a new method for the identification of homing peptide receptors has been developed. An investigation of drug-CREKA conjugates for in the treatment of breast tumors in mice has been initiated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA427172
Entities
People
- Lianglin Zhang
Organizations
- Sanford Burnham Prebys Medical Discovery Institute