单克隆抗体(HIM6)与阿糖胞苷免疫偶合物的研究

Studies of Two Conjugates of Monoclonal Antibody (HIM6) and Cytosine Arabinoside

用葡聚糖和聚谷氨酸为中间载体,将鼠抗人白细胞抗原的单克隆抗体HIM6和阿糖胞苷共价结合,分别形成HIM_6-PAD-ara-C和HIM_6-PLGA-ara-C二个免疫偶合物,其中抗体与药物摩尔比分别为1:15和1:16。二个偶合物与靶细胞HL_(60)的结合能力都与游离单抗基本相同。体外细胞培养显示偶合物对靶细胞的细胞毒作用明显强于对非靶细胞的作用,说明偶合物中单抗特异作用于靶细胞的抗原结合位点,产生特异细胞毒性.

Two conjugates (HIM6-PAD-ara C and HIM6-PLGA-ara C) of the anticancer agent cytosine arabinoside (ara C) and monoclonal antibody (HIM6) against human leukocytes were prepared with dextran T-40 and poly-L-glutamic acid as intermediate carriers,respectively.The drug-antibody conjugates maintained most of the original antigen-binding activity of the free antibody.The ratio of positive bound cells was found to be >90% by an indirect immunofluorescence assay.The cytotoxicities of HIM6-PAD-ara C and HIM6-PLGA-ara C against antibody-reactive human leukemia HL60 cells were lower than those of free ara C and a mixture of ara C and HIM6 (IC50s of HIM6-PAD-ara C,HIM6-PLGA-ara C,ara C and the mixture of ara C and HIM6 were 0.212,0.102,0.028 and 0.024μg/ml,respectively), but were similar to those of the intermediates PAD-ara C and PLGA-ara C. On the other hand,these two conjugates showed no cytotoxic its against non-target hepatoma cells.These results indicate that the specific cytotoxicity of the conjugate depends on specific binding to the target surface antigen by the monoclonal antibody in the conjugate molecule.