PRELIMINARY IN-VITRO EFFICACY AND TOXICITIES STUDIES OF THE HERPES-SIMPLEX THYMIDINE KINASE GENE SYSTEM FOR THE TREATMENT OF BREAST-CANCER

A novel gene therapy strategy is the use of suicide genes that transfe r a drug sensitivity to cancer cells, We present preliminary in vitro efficacy data and in vivo toxicity data using the herpes simplex thymi dine kinase (HStk) gene for breast cancer, The long-term objective of this project is to develop novel approaches for the treatment of breas t cancer using in vivo retroviral gene transfer, Intraductal breast ca ncer cell line HTB126 transduced by an HStk retroviral vector is effic iently inhibited in vitro after GCV exposure, Further analysis reveale d a bystander effect through which nontransduced HTB126 cells were als o inhibited by GCV when cocultured with HStk-transduced HTB126 cells, In cell mixture experiments if only 1% of the cells in culture contain ed the HStk gene, 83% of the culture could be destroyed, Next safety s tudies were performed, Vector producer cells (VPC) were implanted into the mammary fat pads of athymic nude mice, The mice were then treated with GCV and monitored for regression of the VPC, The injected VPC re gressed rapidly in response to the GCV therapy and produced no evidenc e of local or systemic toxicity in the animals, These in vitro efficac y data and in vivo toxicity studies lend support to the further develo pment of an in vivo therapy model to treat breast cancer.