INHIBITION OF EPSTEIN-BARR-VIRUS-TRANSFORMED HUMAN CHRONIC LYMPHOCYTIC LEUKEMIC B-CELLS WITH MONOCLONAL-ANTIBODY ADRIAMYCIN (DOXORUBICIN) CONJUGATES

The anthracyclin antineoplastic agent doxorubicin (Adriamycin) was lin ked by four different methods of linkage to DalB02, an IgG1 kappa muri ne monoclonal antibody (mAb) against surface-associated antigens on hu man chronic lymphocytic leukaemia (CLL) B cells. All the four conjugat es fully retained the immunoreactivity of the parent DalB02. When the inhibitory effect of these conjugates was evaluated in vitro against t he target D-10-1, cells (a clone derived from an Epstein-Barr-virus-tr ansformed human CLL B cell line that binds DalB02) it was observed tha t one conjugate was more potent than the free drug but the others were not. When I-131-labelled unmodified DalB02 and the I-131-labelled Dal B02-containing conjugate that was found to be potent were injected i.v . into nude mice bearing a subcutaneous D-10-1 xenograft, the percenta ges of the injected dose (% ID) of both I-131-DalB02 and the I-131-Dal B02-containing conjugate that localized in the tumour were much higher than the %ID of the respective preparations that localized in normal tissues of D-10-1-xenografted mice. The systemic toxicity of the conju gate was less than that of the free drug. At an equitoxic dose level, this conjugate was a more effective inhibitor of established D-10-1 xe nografts than the free drug.