Anthracycline immunoconjugates prepared by a site-specific linkage via an amino-dextran intermediate carrier.
Anthracycline, either daunomycin or doxorubicin, was site specifically attached to the carbohydrate moiety of a monoclonal anticarcinoembryonic antigen antibody by using amino-dextran as the intermediate carrier. The reaction resulted in an immunoconjugate that contains approximately 20 to 25 molecules of drug per molecule of immunoglobulin G. Flow-cytometric studies revealed the retention of the antibody-binding activity. The immunoconjugate was cytotoxic to the target cells, as examined by the 75selenomethionine incorporation studies, and remained efficient for targeting a human colonic tumor (GW-39) in the nude mouse model. The conjugate possessed a greater antitumor activity against the subcutaneous tumor than either the free drug or an irrelevant antibody conjugate, and it was well tolerated by the animals at a much higher dose level than was the unconjugated drug.
Shih
L B
LB
Garden State Cancer Center, Newark, New Jersey.
Goldenberg
D M
DM
Xuan
H
H
Lu
H
H
Sharkey
R M
RM
Hall
T C
TC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003630:Daunorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004337:Drug Carriers; D004355:Drug Stability; D006801:Humans; D000922:Immunotoxins / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D007202:Indicators and Reagents; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014316:Tritium
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D004337:Drug Carriers; D000922:Immunotoxins; D007202:Indicators and Reagents; D014316:Tritium; D004317:Doxorubicin; D003630:Daunorubicin