Antibody directed enzyme prodrug therapy (ADEPT): a three phase system.
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.
Sharma
S K
SK
Department of Medical Oncology, Charing Cross Hospital, London, U.K.
Bagshawe
K D
KD
Springer
C J
CJ
Burke
P J
PJ
Rogers
G T
GT
Boden
J A
JA
Antoniw
P
P
Melton
R G
RG
Sherwood
R F
RF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006063:Chorionic Gonadotropin / Q000276:immunology; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011355:Prodrugs / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011623:gamma-Glutamyl Hydrolase / Q000008:administration & dosage / Q000493:pharmacokinetics
D000911:Antibodies, Monoclonal; D006063:Chorionic Gonadotropin; D011355:Prodrugs; D011623:gamma-Glutamyl Hydrolase