PREPARATION AND CHARACTERIZATION OF A WATER-SOLUBLE DEXTRAN IMMUNOCONJUGATE OF DOXORUBICIN AND THE MONOCLONAL-ANTIBODY (ABL-364)

An immunoconjugate consisting of the monoclonal antibody ABL 364 and t he cytostatic drug doxorubicin using oxidized dextran as a carrier has been synthesized. Dextran, activated by sodium periodate oxidation, y ielded, 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, p reserved 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 a ntibody ABL 364 and the non-reduced doxorubicin conjugate was prepared . This hybrid molecule retained binding capacity to human breast carci noma (SKBr5) target cells. The in vitro cytotoxic activity was only 2- 3 times lower than for free doxorubicin. Possible modes of action of t he immunoconjugate are discussed to explain its lack of selectivity in the cytotoxicity tests.