Antibody-directed enzyme prodrug therapy (ADEPT) with mustard prodrugs.
Antibody-directed enzyme prodrug therapy (ADEPT) is a two-step targeting procedure designed to improve the selectivity of anti-tumour agents. The approach is based on the activation of specially designed prodrugs by enzyme-antibody conjugates targeted to tumour-associated antigens. This review concerns ADEPT using nitrogen mustard prodrugs and carboxypeptidase G2 (CPG2) as the activating enzyme. The specific structural features required of the nitrogen mustard prodrugs, their design, syntheses, physicochemical properties, biological characteristics and activation to the corresponding drugs are reviewed. The ADEPT clinical trial with a nitrogen mustard prodrug is also discussed.
Springer
C J
CJ
CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, UK.
Niculescu-Duvaz
I
I
D000818:Animals; D000906:Antibodies / Q000378:metabolism / Q000494:pharmacology; D001711:Biotransformation; D004789:Enzyme Activation; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D000922:Immunotoxins / Q000378:metabolism* / Q000494:pharmacology; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011623:gamma-Glutamyl Hydrolase / Q000008:administration & dosage / Q000378:metabolism*
D000906:Antibodies; D018796:Immunoconjugates; D000922:Immunotoxins; D009588:Nitrogen Mustard Compounds; D011355:Prodrugs; D011623:gamma-Glutamyl Hydrolase