Abstract
Antibody-directed enzyme prodrug therapy (ADEPT) involves two phases. The first is an antibody-enzyme conjugate that localizes to tumor. The second phase is a prodrug that is administered when the enzyme-conjugate has cleared from blood and other nontumor tissues. In the pilot-scale clinical trial, the prodrug has been measured--in the plasma of patients, by liquid chromatography (HPLC) and by liquid chromatography-mass spectrometry (LC-MS). Active drug has been detected and metabolites identified. An indirect measurement of enzyme-conjugate in the plasma of patients has also been developed.
Publication types
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Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / blood
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Antibodies, Monoclonal / therapeutic use
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Benzoates* / blood
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Benzoates* / metabolism*
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Benzoates* / pharmacology*
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Chromatography, High Pressure Liquid
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Glutamates / blood
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Glutamates / metabolism*
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Glutamates / pharmacology*
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Humans
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Immunotoxins / blood
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Immunotoxins / therapeutic use*
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Mass Spectrometry
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Mice
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Nitrogen Mustard Compounds / blood
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Nitrogen Mustard Compounds / metabolism*
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Nitrogen Mustard Compounds / pharmacology*
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Prodrugs / metabolism*
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Prodrugs / therapeutic use
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gamma-Glutamyl Hydrolase / blood
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gamma-Glutamyl Hydrolase / therapeutic use
Substances
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Antibodies, Monoclonal
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Benzoates
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Glutamates
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Immunotoxins
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Nitrogen Mustard Compounds
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Prodrugs
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4-((2-chloroethyl) (2-mesyloxyethyl)amino)benzoic acid
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4-((2-chloroethyl)(2-mesyloxyethyl)amino)benzoylglutamic acid
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gamma-Glutamyl Hydrolase