摘要
分别用12.5％、25.0％、50.0％、75.0％和100.0％氧化的Dex T_(10)作为交联剂交联抗人胸腺细胞球蛋白(AHTG)和柔红霉素(DNR)形成免疫偶联物(AHTG-Dex-DNR),其中以25.0％氧化的DexT10作为交联剂最佳。它既提高了偶联物的交联度,又降低了硼氢化钠对AH-TG和DNR活性的损伤。偶联物对靶细胞CEM 24h细胞毒试验LD_(50)为10.68μg/ml。对非靶细胞K562仅有轻微杀伤作用,10min细胞毒试验为特异的杀灭肿瘤细胞试验,对CEM的LD_(50)为14.79μg/ml,对K562几乎无细胞毒作用,表明免疫偶联物有特异性细胞毒作用。
12.5%, 25.0%, 50.0%, 75.0% and 100.0% oxidized dextran (Dex TIO) were used as intermediate carriers for conjugating drug daunorubicin (DNR) and antibody anti-human thymocitic globulin (AHTG), to form an immunoconjugate, AHTG-Dex-DNR. It was demonstrated that the conjugate with 25.0% oxidized DexT10 as an intermediate carrier linked more DNR molecules than the other conjugates. The degree of its substitution was 10-11 moles of DNR per mole of AHTG. Moreover, because the amount of reducing agent, sodium borohydride (NaBH4), required for the reduction reaction was relatively small, its damaging effect on AHTG and DNR was lessened accordingly. The antitumor effect of AHTG-Dex-DNR in vitro was tested by using 24-h cytotoxicity assay, with CEM as target cell. Cytotoxic effect of the conjugate was proven with the LD50 being 10.68 μg/ml. However, it produced only slight cytotoxic effect on non-target cell K562. When 10-min cytotoxicity assay was performed to manifest its specific tumor-killing effect, an obvious cytotoxic CEM was observed with the LD50 being 14.79 μg/ml, but hardly on K562. These results suggest that AHTG-Dex-DNR possesses specific cytotoxic effect.
出处
《同济医科大学学报》
CSCD
北大核心
1992年第4期230-233,共4页
Acta Universitatis Medicinae Tongji
关键词
免疫偶联物
球蛋白
柔红霉素
immunoconjugate
AHTG
daunorubicin
cell lines
