Developments with targeted enzymes in cancer therapy

Cancer therapy based on the delivery of enzymes to tumour sites has advance d in several directions since antibody-directed enzyme/prodrug therapy was first described. It has been shown that methoxypolyethylene glycol (MPEG) c an be used to deliver enzyme to a variety of solid tumours. MPEG-enzyme con jugates show reduced immunogenicity and may allow repeated treatment with e nzymes of bacterial origin. Enzyme delivery to tumours by polymers can be u sed to convert a low toxicity prodrug to a potent cytotoxic agent. An examp le of such a prodrug is CB1954, which can be activated by a human enzyme in the presence of a cosubstrate, Tumour-located enzymes can also be used in conjunction with a combination of antimetabolites and rescue agents. The re scue agent protects normal tissue but is degraded at cancer sites by the en zyme, thus deprotecting the tumour and allowing prolonged antimetabolite ac tion.