Abstract
An immunoconjugate consisting of the monoclonal antibody ABL 364 and the cytostatic drug doxorubicin using oxidized dextran as a carrier has been synthesized. Dextran, activated by sodium periodate oxidation, yielded, after reaction with 3 '-amino group of doxorubicin, a conjugate which was stable under the conditions used thus allowing the omission of the usually applied reduction step. Doxorubicin in the non-reduced conjugate, contrary to the partially or totally reduced homologues, preserved its cytotoxic activity integrally. The feasibility of the ABL 364 coupling to oxidized dextran without loss of its immunoreactivity was demonstrated. Finally an immunoconjugate between the monoclonal antibody ABL 364 and the non-reduced doxorubicin conjugate was prepared. This hybrid molecule retained binding capacity to human breast carcinoma (SKBr5) target cells. The in vitro cytotoxic activity was only 2–3 times lower than for free doxorubicin. Possible modes of action of the immunoconjugate are discussed to explain its lack of selectivity in the cytotoxicity tests.
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