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 transfer a drug sensitivity to cancer cells. We present preliminary in vitro efficacy data and in vivo toxicity data using the herpes simplex thymidine kinase (HStk) gene for breast cancer. The long-term objective of this project is to develop novel approaches for the treatment of breast cancer using in vivo retroviral gene transfer. Intraductal breast cancer cell line HTB126 transduced by an HStk retroviral vector is efficiently inhibited in vitro after GCV exposure. Further analysis revealed a bystander effect through which nontransduced HTB126 cells were also inhibited by GCV when cocultured with HStk-transduced HTB126 cells. In cell mixture experiments if only 1% of the cells in culture contained the HStk gene, 83% of the culture could be destroyed. Next safety studies 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 regressed rapidly in response to the GCV therapy and produced no evidence of local or systemic toxicity in the animals. These in vitro efficacy data and in vivo toxicity studies lend support to the further development of an in vivo therapy model to treat breast cancer.
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C J
CJ
Laboratory of Molecular Oncology, Human Gene Therapy Research Institute, Des Moines, IA 50309, USA.
Kolb
E M
EM
Muldoon
R R
RR
D000818:Animals; D001943:Breast Neoplasms / Q000628:therapy*; D002277:Carcinoma / Q000628:therapy*; D002478:Cells, Cultured; D018014:Gene Transfer Techniques / Q000009:adverse effects*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects; D006561:Herpes Simplex / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012190:Retroviridae / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D013937:Thymidine Kinase