Development of Targeted Sindbis Virus Vectors for Potential Application to Breast Cancer Therapy
Abstract
The purpose of the proposed research is to develop a propagation-competent alphavirus vector that is targeted specifically to receptors expressed on breast cancer cells or to receptors expressed on tumor-associated vasculature. We hypothesize that this type of targeted vector would provide a very efficient means of specifically killing a large number of malignant cells. Sindbis virus (sv), an alphavirus, containing a 200 basepair sequence encoding the epidermal-like growth factor domain of heregulin in place of a portion of its receptor-binding domain, is impaired in its ability to assemble and bud from transfected cells. However, a SV containing a 13 amino acid NGR-containing peptide motif is able to replicate and spread i% infected cells. This NGR-containing SV exhibits an ability to more efficiently kill cells expressing the targeted CDl3 receptor compared to parent virus-infected cells. Hence, we have demonstrated that it is possible to generate a propagation-competent Sv containing a targeting ligand. The optimal location(s) for such a ligand within the receptor-binding domain of SV needs to be determined. Subsequently, in vivo studies using mouse tumor models will be performed to determine the ability of such a targeted SV to specifically destroy breast cancer tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA404597
Entities
People
- Lesia Dropulic
Organizations
- Johns Hopkins University