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Anthracycline Immunoconjugates Prepared by a Site-specific Linkage via an Amino-Dextran Intermediate Carrier¹

Garden State Cancer Center and Center for Molecular Medicine and Immunology, Newark, New Jersey 07103

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.

¹ Supported in part by USPHS Grant CA 39841 from the NIH and by Grant 89-240360-6 from the New Jersey Commission on Science and Technology.

² To whom requests for reprints should be addressed, at the Center for Molecular Medicine and Immunology, 1 Bruce St., Newark, NJ 07103.

Received 1/31/91. Accepted 5/31/91.

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