Inhibition of Epstein-Barr-virus-transformed human chronic lymphocytic leukaemic B cells with monoclonal-antibody-adriamycin (doxorubicin) conjugates.
The anthracyclin antineoplastic agent doxorubicin (Adriamycin) was linked by four different methods of linkage to DalB02, an IgG1 kappa murine monoclonal antibody (mAb) against surface-associated antigens on human chronic lymphocytic leukaemia (CLL) B cells. All the four conjugates fully retained the immunoreactivity of the parent DalB02. When the inhibitory effect of these conjugates was evaluated in vitro against the target D10-1 cells (a clone derived from an Epstein-Barr-virus-transformed human CLL B cell line that binds DalB02) it was observed that one conjugate was more potent than the free drug but the others were not. When 131I-labelled unmodified DalB02 and the 131I-labelled DalB02-containing conjugate that was found to be potent were injected i.v. into nude mice bearing a subcutaneous D10-1 xenograft, the percentages of the injected dose (%ID) of both 131I-DalB02 and the 131I-DalB02-containing conjugate that localized in the tumour were much higher than the %ID of the respective preparations that localized in normal tissues of D10-1-xenografted mice. The systemic toxicity of the conjugate was less than that of the free drug. At an equitoxic dose level, this conjugate was a more effective inhibitor of established D10-1 xenografts than the free drug.
Zhu
Z
Z
Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
Kralovec
J
J
Ghose
T
T
Mammen
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000821:virology*; D002455:Cell Division / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects*; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D000922:Immunotoxins / Q000493:pharmacokinetics / Q000494:pharmacology*; D007275:Injections, Intravenous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D004317:Doxorubicin