Enzyme prodrug therapy

摘要

The invention relates to a molecular chimaera for use with a prodrug, the molecular chimaera comprising a transcriptional regulatory DNA sequence capable of being activated in a targetted mammalian cell and a DNA coding sequence operatively linked to the transcriptional regulatory DNA sequence and encoding a secretion signal peptide and a heterologous enzyme, such that on expression of said coding sequence in the targetted cell, the heterologous enzyme is capable of passing through the cell plasma membrane and is capable of catalysing extracellular conversion of the prodrug into a cytotoxic or cytostatic agent. When the molecular chimaera is used in gene or virus directed enzyme prodrug therapy the fact that enzyme is secreted so that conversion of the prodrug to the cytotoxic or cytostatic agent is extracellular increases neighbouring cell kill.