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Identification of prodrug, active drug, and metabolites in an ADEPT clinical study

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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.

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Authors and Affiliations

  1. Department of Medical Oncology, Cancer Research Campaign Laboratories, Charing Cross Hospital, W6 8RF, London, England

    C. J. Springer, Surinder K. Sharma & K. D. Bagshawe

  2. Institute of Cancer Research, Cancer Research Campaign Laboratories, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, England

    C. J. Springer & G. K. Poon

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  1. C. J. Springer
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  2. G. K. Poon
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  3. Surinder K. Sharma
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  4. K. D. Bagshawe
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Springer, C.J., Poon, G.K., Sharma, S.K. et al. Identification of prodrug, active drug, and metabolites in an ADEPT clinical study. Cell Biophysics 22, 9–26 (1993). https://doi.org/10.1007/BF03033864

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