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

Citation
Zp. Zhu et al., INHIBITION OF EPSTEIN-BARR-VIRUS-TRANSFORMED HUMAN CHRONIC LYMPHOCYTIC LEUKEMIC B-CELLS WITH MONOCLONAL-ANTIBODY ADRIAMYCIN (DOXORUBICIN) CONJUGATES, Cancer immunology and immunotherapy, 40(4), 1995, pp. 257-267
Citations number
36
Categorie Soggetti
Immunology,Oncology
ISSN journal
03407004
Volume
40
Issue
4
Year of publication
1995
Pages
257 - 267
Database
ISI
SICI code
0340-7004(1995)40:4<257:IOEHCL>2.0.ZU;2-1
Abstract
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.