Tumor Specific Gene Expression and Tumor Specific Vector Replication for Systematic Chemotherapy Sensitization Treatment of Breast Cancer

摘要

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- Fluorocytosine (5FC), thereby sensitizing the cells in which it is produced to 5FC induced toxicity. We have also generated vectors in 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.