Publication of the International Union Against Cancer Publication de I'Union Internationale Contre le Cancer DOXORUBICIN: MONOCLONAL ANTIBODY CONJUGATE FOR THERAPY OF

Doxorubicin (Dox) was conjugated via a dextran linker to the F(ab')2 fragment of monoclonal antibody (MAb) lHtO which recognizes an antigen expressed on the surface of human ceryical carcinoma cells and tissues. Drug-antibody conjugates(l H!0-Dox) with a molar ratio of Dox to MAb rangihg from 40: I to 60: I rebined antigen-binding and pharmacologlcal activities. Arti-tumor activity of tlre-go4jugate in vitro was evaluated by measuring inhibition of [5-3H]-uridine incorporation into cellu-lar RNA. lHl0-Dox was found to be 30 times more toxic to ceruical tumor cells than a control MAb-Dox conjugate and 150 times more potent than Dox coupled to dextran. ln addition, f Hf0-Dox was less toxic to antigen-negative cells in vitro, suggesting that I H | O-Dox killing of ceryical carcinoma cells was 4tibody-mediated.! 2s|-labeled I H | O-Dox preferentially local-ized in solid human ceryical carcinoma xenografts in athymic mice with tumor-to-blood ratios of lHl0-Dox reaching-17.