Anthracycline immunoconjugates prepared by a site-specific linkage via an amino-dextran intermediate carrier
Shih, L.B.; Goldenberg, D.M.; Xuan, H.; Lu, H.; Sharkey, R.M.; Hall, T.C.
Cancer Research 51(16): 4192-4198
1991
ISSN/ISBN: 0008-5472 PMID: 1868440 Document Number: 373492
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.