The potential of carboxypeptidase G2: antibody conjugates as anti-tumour agents. II. In vivo localising and clearance properties in a choriocarcinoma model.
The in vivo localising and clearance properties of conjugates of the folate-degrading enzyme carboxypeptidase G2 (CPG2) with anti-human chorionic gonadotrophin (W14A) were measured in nude mice bearing CC3 choriocarcinoma xenografts. Conjugates of W14A-F (ab')2 fragment coupled to CPG2 localised in tumour as effectively as native antibody alone but showed lower uptake in other major tissues. The clearance rates of conjugates prepared with intact antibody or F (ab')2 fragment were shown to be up to five-fold faster than for native antibody and two-fold compared to F (ab')2 fragment. Molecular weight analysis of residual conjugate in the blood showed that no degradation of conjugate to its component molecules occurred during circulation. It was concluded that F (ab')2: CPG2 conjugates offered the greatest potential for targeting applications.
Melton
R G
RG
Division of Biotechnology, PHLS Centre for Applied Microbiology and Research, Salisbury, Wilts, UK.
Searle
F
F
Sherwood
R F
RF
Bagshawe
K D
KD
Boden
J A
JA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002822:Choriocarcinoma / Q000378:metabolism / Q000628:therapy*; D006063:Chorionic Gonadotropin / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004337:Drug Carriers; D007140:Immunoglobulin Fab Fragments / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014018:Tissue Distribution; D011623:gamma-Glutamyl Hydrolase / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000911:Antibodies, Monoclonal; D006063:Chorionic Gonadotropin; D004337:Drug Carriers; D007140:Immunoglobulin Fab Fragments; D011623:gamma-Glutamyl Hydrolase; D003546:Cysteine Endopeptidases