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

摘要

The L-plastin promoter has been shown to promote expression of therapeutic and proliferation genes in adenoviral vectors which is tumor specific. In the last year, this grant has supported the study of replication incompetent adenoviral vectors with cytosine deaminase therapeutic genes regulated by the L-plastin promoter. These vectors have been shown in cell lines, primary explant cultures and animal models to be selectively toxic to ovarian and breast cancer cells. Adenoviral vectors with the ElA gene under control of the L-plastin promoter have also been constructed in this grant. These conditionally replication competent vectors have been shown in cell lines and primary explant models to be selectively toxic to breast and ovarian cancer cells. These data suggest that such vectors may be of value for new directions in treatment of breast cancer in advance disease patients. Work to be carried out in the next year include construction of adenoviral vectors in which both the cytosine deaminase and ElA genes are regulated by the L-plastin promoter, and the study of this new vector as well as the conditionally replication competent vectors in which the ElA gene is regulated by the L-plastin promoter in cell lines, primary explant cultures and animal models.