Endothelial Cell-Targeted Adenoviral Vector for Suppressing Breast Tumors

摘要

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 to tumor suppression. The overall goal of this proposal is to develop an adenovirus-based gene therapy approach for suppressing angiogenesis. In the first year of the funding period, we focused our effort on developing the endothelial cell-targeted adenovirus vector. We incorporated five previously published endothelial cell-specific peptide sequences into adenovirus capsid fiber sequence and the modified fibers were added to Beta-galactosidase- containing adenovirus with a helper-cell strategy. We examined the infectivity and specificity on human microvascular endothelial cells and several other cell lines and found that two of the published sequences (NGR and SPARC) were able to facilitate adenoviral vectors specifically and efficiently transducing human endothelial cells. These studies clearly demonstrate that endothelial cell-targeted adenoviral vector can be generated rather simply and easily. In our future studies, we will use our developed vector to deliver anti-angiogenesis genes to tumor vascular structure and to evaluate the efficacy of these vectors to suppress breast tumor development in both in vitro and in vivo models.