Antibody-Directed Enzyme Prodrug Therapy
Antibody-directed enzyme prodrug therapy (ADEPT) was conceived as a means of reducing the toxicity of chemotherapy and improving its efficacy by generating the cytotoxic agent at tumor sites (Figure 1). It was proposed that this could be done by using an antibody directed at a tumor-associated antigen to convey an enzyme to tumor sites and, when the enzyme had cleared from the blood, to give a low toxicity prodrug from which a high toxicity drug would be released by enzymic catalysis within tumors. The active drug would be a small molecule able to diffuse within a tumor and thus overcome the heterogeneity in tumor marker expression that was seen as a potential limitation to conjugates of cytotoxic agents and antibodies. At the outset it was envisaged that the antibodyenzyme complex could be genetically engineered and that the drug generated would have a very short half-life (Bagshawe, 1987).
KeywordsCytosine Deaminase Enzyme Prodrug Therapy Radiolabelled Antibody Antibody Direct Enzyme Prodrug Therapy London Group
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