Targeted Therapy of Fn14-Positive Breast Tumors Using a TWEAK-Cytotoxin Fusion Protein or Noncovalent Complex
Abstract
Our laboratory research is focused on the potential roles of a TNF-related cytokine named TWEAK and its specific cell surface receptor named Fn14 in tumor biology. We reported previously that the Fn14 gene is highly expressed in many human breast cancers. In this Breast Cancer Concept Award application we proposed to investigate whether we could make Fn14-targeted toxins that would kill Fn14-positive breast cancer cells in vitro and in vivo. Our most significant findings during the one-year research period are that although TWEAK-based single chain or two chain non-covalently linked toxins do have some cytotoxicity on cancer cells this approach is not ideal because of protein aggregation issues, likely problems with translating these molecules to clinical use, and the recent identification of a second TWEAK-binding protein. A different approach, namely using an Fn14 mAb to deliver toxic cargo, appears to be a better strategy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2010
- Accession Number
- ADA541956
Entities
People
- Jeffrey A. Winkles
- Sharron Brown
Organizations
- University of Maryland, Baltimore