Tumor Specific Gene Expression and Tumor Specific Vector Replication for Systemic Chemotherapy Sensitization Treatment of Breast Cancer
Abstract
We have developed a safety modified adenoviral vector in which the tumor specific L- plastin promoter can be used to control the expression of therapeutic genes such as cytosine deaminase (CD) . The CD gene product catalyzes the conversion of a non-toxic precursor, 5-Fluorocytosine (5FC) into a drug, 5-Fluorouracil (5FU), thereby sensitizing the cells in which it is produced to SFC induced toxicity. We have also generated vectors in which the L-plastin promoter is used to drive the expression of the viral ElA gene, which the adenovirus needs to replicate within mammalian cells. The replication of a virus within a mammalian cell takes over all of the metabolic and cell proliferative machinery of the cells and thereby kills it. Our data shows that the adenoviral vector which carries the L-plastin-ElA transcription unit can replicate within breast cancer cells and other estrogen dependent carcinomas, such as ovarian cancer, while not being able to replicate in normal cells. This L-plastin-ElA vector can suppress the growth of human breast cancer cell lines in immunosuppressed mice. We have recently isolated a vector in which both the CD ElA genes are under the control of the L-plastin promoter, which is currently under study.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396709
Entities
People
- Albert B. Deisseroth
Organizations
- Yale University