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 molecu...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1991-08, Vol.51 (16), p.4192-4198
Main Authors: Shih, L B, Goldenberg, D M, Xuan, H, Lu, H, Sharkey, R M, Hall, T C
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - pharmacokinetics
Antibodies, Monoclonal - pharmacology
Antibodies, Monoclonal - therapeutic use
Carcinoembryonic Antigen - immunology
Cell Line
Cell Survival - drug effects
Colonic Neoplasms - drug therapy
Daunorubicin - pharmacology
Daunorubicin - therapeutic use
Doxorubicin - pharmacokinetics
Doxorubicin - pharmacology
Doxorubicin - therapeutic use
Drug Carriers
Drug Stability
Humans
Immunotoxins - chemical synthesis
Immunotoxins - pharmacokinetics
Immunotoxins - pharmacology
Immunotoxins - therapeutic use
Indicators and Reagents
Mice
Mice, Nude
Neoplasm Transplantation
Tissue Distribution
Transplantation, Heterologous
Tritium
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Summary: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.
ISSN:0008-5472