Peptide-Targeted Drug Delivery to Breast Tumors
Abstract
Our proposal is aimed at using a genetic selection/screening technique to identify peptides that selectively recognize breast cancer cells (as opposed to normal cells of the same or different type). Such cancer-specific peptides will then be coupled to flexile-based long-circulating drug carriers to confer upon these compounds the desired specificity. In the first year of our work, we optimized conditions and screened phage display libraries for peptides that selectively bind to Erb2, an important cell surface receptor overexpressed in breast cancer cells. Unfortunately, all peptides lost specificity of binding, when assayed independently from the phages. The challenge for the second year was to identify peptides that retain binding specificity when tested separately from the phage with which they were identified. As a more powerful method to identify Erb2-binding peptides, we have undertaken phage panning experiments with purified extra cellular domain of the Erb2 protein produced in a soluble form. At the same time, we have started to produce recombinant EGF and Heregulin 1, which are well known ligands of Erb2 when paired with the EGF receptor and Erb3, respectively. The recombinant EGF and Heregulin will then be coupled to macro molecular carriers for binding to Erb2 over expressing breast carcinoma cells, as for the experiments planned for the peptides.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA373913
Entities
People
- Gian P. Dotto
Organizations
- Massachusetts General Hospital