Antibody directed enzyme prodrug therapy (ADEPT): a three phase system

Dis Markers. 1991 May-Aug;9(3-4):225-31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Chorionic Gonadotropin / immunology
  • Mice
  • Neoplasm Transplantation
  • Neoplasms, Experimental / drug therapy*
  • Prodrugs / administration & dosage*
  • Prodrugs / pharmacokinetics
  • gamma-Glutamyl Hydrolase / administration & dosage
  • gamma-Glutamyl Hydrolase / pharmacokinetics

Substances

  • Antibodies, Monoclonal
  • Chorionic Gonadotropin
  • Prodrugs
  • gamma-Glutamyl Hydrolase