USE OF TRANSCRIPTIONAL REGULATORY ELEMENTS OF THE MUC1 AND ERBB2 GENES TO DRIVE TUMOR-SELECTIVE EXPRESSION OF A PRODRUG ACTIVATING ENZYME

In order to exploit differences in gene expression between normal and malignant cells for genetic prodrug-activation therapy, we have genera ted recombinant retroviruses containing the herpes simplex virus thymi dine kinase coding region cloned downstream of sequences derived from the 5'-flanking regions of the MUC1 and ERBB2 genes. Transduction with retroviruses containing MUC1 promoters resulted in an increase in GCV sensitivity in MUC1-positive cells. A further increase in GCV sensiti vity was achieved when MUC1-positive cells were transduced with retrov iruses containing chimeric MUC1/ERBB2 promoters. No significant sensit ization to GCV was observed when MUC1-negative cells were transduced w ith these recombinant retroviruses. These results suggest that one may be able to develop a tumour-selective therapy by utilizing the transc riptional regulatory regions of the MUC1 and ERBB2 genes to drive the expression of suicide genes.