Advanced drug delivery reviews: enzyme prodrug therapy

• Published in: Advanced drug delivery reviews 1996-12, Vol.22 (3), p.269-288
• Main Author: Sherwood, Roger F.
• Format: Article
• Language: English
• Subjects: ADEPT; Antineoplastic agents; Biological and medical sciences; Cancer; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Enzyme; GDEPT; Medical sciences; Pharmacology. Drug treatments; Prodrug; Targeting; VDEPT
• ISSN: 0169-409X; 1872-8294
• DOI: 10.1016/S0169-409X(96)00450-4

Enzymes have provided a focus for the chemist to design a range of prodrugs to release cytotoxic agents already in use in the cancer clinic and those which had been candidates in the past, based on their efficacy in preclinical studies, but discarded because of their toxicity to normal tissues. The specificity of enzyme reactions provides the means to limit prodrug activation to the tumour site, through enzyme targeting by chemical conjugation or genetic fusion to tumour associated antibodies (ADEPT), or via enzyme gene delivery systems into tumour cells (GDEPT). The substrate tolerance of many of the enzymes used has also meant that a variety of prodrug/drug combinations can be assessed using the same enzyme reaction. It is the flexibility provided by the choice of enzyme, the range of tumour antigen targets and the prodrug chemistry that makes ADEPT such an exciting prospect for the future of cancer treatment and the more recent extension of the enzyme/prodrug concept to a gene therapy approach provides a second avenue for success.