含有篦麻毒素和阿霉素的双弹头免疫毒素的构建及其杀伤活性

本文用化学偶联方法,将篦麻毒素(RiCin)及阿霉素(Adriamycin,Adr)同时偶联到抗人膀胱癌单克隆抗体分子上,构建了第一个具有“双单头”的抗肿瘤导向药物。经间接免疫荧光检测以及放射竞争结合试验证明,这个免疫毒素保持了原抗体活性的70%。体外杀伤试验的结果表明,这个双单头免疫毒素在0.1M半乳糖存在的条件下,对膀胱癌细胞BIU-87的体外杀伤作用比单抗-阿霉索强30000倍;比单抗-篦麻毒素强10倍。对无关的人直肠癌LoVo细胞无明显的杀伤作用。

Construction and cytotoxicity of two-killing-agent immunotoxin containing Ricin and Adriamycin

The synergistic effect of combinations of killing agents on tumor cells has long been recognized. Fodstad et al, reported that the combinations of Ricin and Adriamycin have a strong, syn ergistic effect on the L1210 leukemia cells. In this report, a novel immunotoxin containing Ricin and Adriamycin, BDI-l-Ricin-Adriamycin, was described.Ricin and Adriamycin were chemically coupled onto one monoclonal antibody molecule against human bladder cancer, BDI-1, to construct the two-killing-agent containing immunotoxin. The results of indirect immunofluorescence test and competiton bindig assay showed that the retention of 70% of the antibody binding activity in this immunotoxin was obtained. The in vitro cytotoxicity assay indicated that the immunotoxin in the presence of 0.1M galactose is 30,000 times more cytotoxic than BDI-1-Adriamycin conjugate and 10 times more cytotoxic than BDI-1-Ricin immunotoxin in the bladder cancer-specific killing, but has no cytotoxic effect on the LOVO colon carcinoma cells. This two-killing-agent containing immunotoxin may lead to the development of a new kind of immunotoxins which have strong cytotoxic activity to target cells.