Targeting: The ADEPT Story So Far

K.   D.   Bagshawe

Abstract

Antibody-directed enzyme prodrug therapy aims to restrict the action of a cytotoxic drug to cancer sites. An enzyme that has no human analogue is delivered to cancer sites by attachment to an antibody directed at a tumour associated antigen. In a second step an antibody or other agent inactivates and clears enzyme from blood. The third step is administration of a low toxicity prodrug that is a substrate for the enzyme thus generating a potent cytotoxic agent at cancer sites. Encouraging results were obtained with this system in small scale clinical trials using unrefined agents. During the past 10 years attempts have been made to reduce the system to two components. Although these have met with some success it is now accepted that future progress requires all three components.

Keywords: ADEPT, antibody, enzyme, prodrug, fusion proteins, cancer therapy

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