Zhu Z, Kralovec J, Ghose T, Mammen M
Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
Cancer Immunol Immunother. 1995 Apr;40(4):257-67. doi: 10.1007/BF01519900.
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.
蒽环类抗肿瘤药物阿霉素（阿霉素）通过四种不同的连接方法与DalB02相连，DalB02是一种针对人类慢性淋巴细胞白血病（CLL）B细胞表面相关抗原的IgG1κ小鼠单克隆抗体（mAb）。所有四种缀合物都完全保留了亲本DalB02的免疫反应性。当在体外评估这些缀合物对靶标D10-1细胞（一种源自爱泼斯坦-巴尔病毒转化的人类CLL B细胞系且能结合DalB02的克隆）的抑制作用时，发现一种缀合物比游离药物更有效，但其他缀合物则不然。当将131I标记的未修饰DalB02和被发现有效的含131I标记DalB02的缀合物静脉注射到携带皮下D10-1异种移植物的裸鼠体内时，131I-DalB02和含131I-DalB02的缀合物在肿瘤中定位的注射剂量百分比（%ID）远高于在D10-1异种移植小鼠正常组织中定位的各自制剂的%ID。缀合物的全身毒性低于游离药物。在等毒性剂量水平下，这种缀合物比游离药物更有效地抑制已建立的D10-1异种移植物。
