Endothelial Cell-Targeted Adenoviral Vector for Suppressing Breast Malignancies
Abstract
Angiogenesis is essential for the growth and metastasis of solid tumors including breast cancer. In vitro and in vivo experimental models clearly demonstrate that suppressing angiogenesis leads tumor suppression. The overall goal of this proposal is to develop an adenovirus-based gene therapy approach for suppressing angiogenesis. In first year of the funding period, we have successfully constructed a human endothelial cell-targeted adenovirus gene delivery vector. In this second year of funding period, we successfully constructed endothelial cell-targeted adenoviral vector containing therapeutic genes including soluble VEGF receptor (sFlk and sFlt) and dominant negative angiogenesis-essential signaling molecules including Raf-1 and PI-3K. These vectors were found to significantly inhibit VEGF-induced human endothelial cell migration and in vitro angiogenesis. In the last year of the funding, we have focused on our effort to determine whether the endothelial cell-targeted adenoviral vector can be used to deliver anti-angiogenesis agents to block angiogenesis and tumor development in animal models. Our studies demonstrate that our approach can sufficiently inhibit both angiogenesis and breast tumor development. We believe that our endothelial cell target adenoviral vector provide a useful means for specifically delivering therapeutic agents to angiogenic tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA436940
Entities
People
- Shuang Huang
Organizations
- Scripps Research