A fluorouridine-anti-CEA immunoconjugate is therapeutically effective in a human colonic cancer xenograft model.
5-fluorouridine (FUR), an antineoplastic agent, was site-specifically conjugated to the carbohydrate moiety of a anticarcinoembryonic antigen (CEA) monoclonal antibody (MAb) by using amino-dextran as the intermediate carrier. The final immunoconjugate contains approximately 30-35 molecules of FUR per molecule of immunoglobulin, has immunoreactivity retained as examined by flow cytometry, and is cytotoxic to the target cells as examined by 75selenomethionine incorporation studies. In the GW-39/nude mouse model, the conjugate remained efficient in targeting the human colonic tumor and possessed greater inhibitory growth effects on the subcutaneous tumor than free FUR or an irrelevant antibody conjugate. In addition, the reduced host toxicity of the conjugate may permit the use of this agent in a high-dose therapy of this tumor system.
Center for Molecular Medicine and Immunology, UMDNJ, Newark 07103.
L B
LB
Shih
H
H
Xuan
R M
RM
Sharkey
D M
DM
Goldenberg
D000818:Animals; D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003911:Dextrans; D004337:Drug Carriers; D006801:Humans; D007141:Immunoglobulin Fc Fragments; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D002272:Carcinoembryonic Antigen; D003911:Dextrans; D004337:Drug Carriers; D007141:Immunoglobulin Fc Fragments; C001943:5-fluorouridine; D014529:Uridine