EX-VIVO BREAST-CANCER CELL PURGING BY ADENOVIRUS-MEDIATED CYTOSINE DEAMINASE GENE-TRANSFER AND SHORT-TERM INCUBATION WITH 5-FLUOROCYTOSINE COMPLETELY PREVENTS TUMOR-GROWTH AFTER TRANSPLANTATION

Peripheral blood progenitor harvests of breast cancer patients are con taminated with tumor cells, suggesting a potential role for these cell s in the relapse after high-dose chemotherapy, Whereas physical purgin g methods do not eliminate contaminating tumor cells completely, pharm acological purging, although highly efficient, is hampered by a strong nonspecific toxicity toward hematopoietic progenitor cells. Taking ad vantage of the high efficiency of adenovirus-mediated gene transfer to epithelial cells, we selectively loaded breast cancer cells in vitro with a cytotoxic drug by gene transfer of the prodrug-converting enzym e cytosine deaminase (AdCMV.CD) and 5-fluorocytosine (5-FC). Despite t he low dose of vector administered, limited exposure to 5-FC, and tran splantation only of viable tumor cells into SCID mice, all animals tha t received cells treated in vitro with AdCMV.CD plus 5-FC were complet ely free of tumor development. These data show that the selective load ing of tumor cells with AdCMV.CD/5-FC might be useful for purging of a utografts.