Doxorubicin-anti-carcinoembryonic antigen immunoconjugate activity in vitro.
An in vitro model consisting of a series of 11 human cancer cell lines with varying density of expression of membrane carcinoembryonic antigen (CEA) has been used to evaluate conjugates of doxorubicin (Adriamycin) covalently linked by a carbodiimide method to goat polyclonal antibodies and mouse monoclonal antibodies to CEA. Conjugates were produced which retained both antigen binding and drug cytotoxicity. IC50 values were determined for free drug, free drug mixed with unconjugated antibodies and for the immunoconjugates. Cell lines that were very sensitive to free drug (IC50 less than 100 ng/ml) were also found to be highly sensitive to conjugated drug and similarly cell lines resistant to drug (IC50 greater than 1,000 ng/ml) were also resistant to conjugated drug. Although there was no correlation between CEA expression and conjugates efficacy, competitive inhibition studies using autologous antibody to block conjugate binding to cells indicated immunoconjugates specificity for the CEA target.
Richardson
V J
VJ
Memorial University of Newfoundland, St John's, Canada.
Ford
C H
CH
Tsaltas
G
G
Gallant
M E
ME
D000906:Antibodies / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D004337:Drug Carriers; D004317:Doxorubicin