Enhancing Anti-Breast Cancer Immunity by Blocking Death Receptor DR5
Abstract
The original hypothesis was that blocking DR5 with vaccine-induced antagonist antibodies (Ab) will protect T cells from TRAIL-induced apoptosis and enhance their anti-tumor activity. The three specific aims were to (1) Construct and test DR5 vaccines to induce anti-DR5 Ab (2) Test the antagonist activity of vaccine-induced anti-DR5 Ab and (3) Amplify anti-tumor immunity by DR5 vaccination. We found that immune sera to human DR5 showed significant agonist rather than antagonist activity to induce profound tumor cell apoptosis. Histone deacetylase induced the expression of TRAIL in tumor cells via SP-1 and may be used to complement DR5 vaccination. Furthermore activated T cells were resistant to DR5 mediated apoptosis. Based on these interesting results we will proceed with the revised hypothesis that agonist DR5 Ab induced by DNA vaccination will trigger tumor cell apoptosis without compromising T cell activity. The specific aims are to (1) Construct and test DR5 vaccines to induce anti-DR5 Ab (2) Test the agonist activity of vaccine-induced anti-DR5 Ab and (3) Amplify anti-tumor activity of DR5 vaccination with novel chemotherapeutics.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2008
- Accession Number
- ADA494599
Entities
People
- Wei-Zen Wei
Organizations
- Wayne State University