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Inhibition of Epstein-Barr-virus-transformed human chronic lymphocytic leukaemic B cells with monoclonal-antibody-Adriamycin (doxorubicin) conjugates

  • Original Article
  • Monoclonal Antibody, Adriamycin, Immunoconjugates, Chronic Lymphocytic Leukaemia, Tumor Inhibition
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Abstract

The anthracyclin antineoplastic agent doxorubicin (Adriamycin) was linked by four different methods of linkage to DalB02, an IgG1κ 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. When131I-labelled unmodified DalB02 and the131I-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 both131I-DalB02 and the131I-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.

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Author notes

  1. Zhenping Zhu

    Present address: Department of Cell Genetics, Genentech Inc., 460 Point San Bruno Blvd., 94080, South San Francisco, CA, USA

Authors and Affiliations

  1. Department of Pathology, Dalhousie University, Sir Charles Tupper Medical Building, B3H 4H7, Halifax, Nova Scotia, Canada

    Zhenping Zhu, Jaroslav Kralovec, Tarunendu Ghose & Molly Mammen

  2. Department of Microbiology and Immunology, Dalhousie University, B3H 4H7, Halifax, Nova Scotia, Canada

    Zhenping Zhu

Authors
  1. Zhenping Zhu
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  2. Jaroslav Kralovec
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  3. Tarunendu Ghose
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  4. Molly Mammen
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Additional information

This study was supported by grants from the Medical Research Council of Canada (grant MT 10964) and the Cancer Research Society Inc., Montreal, Canada

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Zhu, Z., Kralovec, J., Ghose, T. et al. Inhibition of Epstein-Barr-virus-transformed human chronic lymphocytic leukaemic B cells with monoclonal-antibody-Adriamycin (doxorubicin) conjugates. Cancer Immunol Immunother 40, 257–267 (1995). https://doi.org/10.1007/BF01519900

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  • DOI: https://doi.org/10.1007/BF01519900

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