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以氧化葡聚糖法制备了阿霉素(ADM)与胃癌单克隆抗体(MoAb)3H11的交联物3H11-DEX-ADM,ADM与3H11克分子比为73:1。经ELISA法测定,交联物的抗体活性保留86％。体外细胞毒试验显示,3H11-DEX-ADM对胃癌细胞BGC823的杀伤作用比游离ADM明显增强,其IC_(50)分别为1.0μg/ml及3.75μg/ml。在荷瘤裸鼠治疗实验中3H11-DEX-ADM能显著抑制肿瘤生长,抑制率为51.5％(P<0.05),明显高于ADM组及其非特异性抗体交联物(NI gG-DEX-ADM)组,后者的抑制率分别为21％及24％。表明3H11-DEX-ADM对肿瘤具有选择杀伤作用。将3H11-DEX-ADM与丝裂霉素C(MMC)-3H11交联物(3H11-HSA-MMC)联合应用,细胞素实验未能显示协同或相加作用;游离ADM与MMC联合亦呈相似结果。
The cross-linked product 3H11-DEX-ADM of doxorubicin (ADM) and gastric cancer monoclonal antibody (MoAb) 3H11 was prepared by oxidized dextran method. The molar ratio of ADM to 3H11 was 73: 1. Antibody activity of the cross-linked product was retained by 86% as determined by ELISA. In vitro cytotoxicity assay showed that the killing effect of 3H11-DEX-ADM on gastric cancer cells BGC823 was significantly enhanced compared with that of free ADM. The IC 50 of them were 1.0μg / ml and 3.75μg / ml, respectively. 3H11-DEX-ADM could significantly inhibit tumor growth in tumor-bearing nude mice with the inhibition rate of 51.5% (P <0.05), which was significantly higher than that of ADM and its non-specific antibody conjugate (NI gG-DEX-ADM ) Group, the latter inhibition rate was 21% and 24%. This indicated that 3H11-DEX-ADM has a selective killing effect on the tumor. The combination of 3H11-DEX-ADM with mitomycin C (MMC) -3H11 conjugate (3H11-HSA-MMC) did not show synergistic or additive effects; the combination of free ADM and MMC was also similar result.