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  • Title: Antibody directed enzyme prodrug therapy (ADEPT): a three phase system.
    Author: Sharma SK, Bagshawe KD, Springer CJ, Burke PJ, Rogers GT, Boden JA, Antoniw P, Melton RG, Sherwood RF.
    Journal: Dis Markers; 1991; 9(3-4):225-31. PubMed ID: 1813212.
    Abstract:
    Monoclonal anti-CEA antibody, A5B7, and its fragments conjugated to CPG2 localize to a peak concentration in the LS174T xenografts within 24 h after injection, but enzyme activity persists in plasma such that prodrug injection has to be delayed for 5-6 days in order to avoid toxicity. Injection of prodrug at this time did not result in growth delay of this tumour. A three-phase system has been developed in which residual plasma enzyme was inactivated and cleared by a galactosylated anti-CPG2 antibody, SB43gal, allowing prodrug administration within 24 h after the conjugate. Using this three-phase system, a marked growth delay of this tumour was achieved after a single course of treatment consisting of conjugate injection followed by SB43gal, 19 h later and three doses of the prodrug.
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