肝癌单抗JH11－ADM交联物的制备及其细胞毒作用

Preparation and the Cytotoxicities of Conjugates Composed of Adriamycin and Monoclonal Antibody against Liver Cancer

以葡聚糖（Ｄｅｘ）为中间载体，通过碘酸氧化法制备阿霉素（ＡＤＭ）与肝癌单抗ＪＨ１１的交联物ＡＤＭ－Ｄｅｘ－ＪＨ１１，交联物中ＡＤＭ与ＪＨ１１的克分子比为７１：１．经ＩＦＡ测定交联物的抗体活性大部分保持。体外细胞毒试验显示，ＡＤＭ－Ｄｅｘ－ＪＨ１１对ＢＥＬ－７４０２细胞的杀伤作用比游离的ＡＤＭ强．其ＩＣ５０分别为０．９６μｇ／ｍｌ和１．５２μｇ／ｍｌ，对非靶细胞ＭＧｃ－８０３和Ｌ３４２的毒性很弱，它们的ＩＣ５０＞１０μｇ／ｍｌ．集落形成抑制试验表明，ＡＤＭ－Ｄｅｘ－ＪＨ１１在低浓度时即对ＢＥＬ－７４０２集落形成有显著抑制作用，ＩＣ５０为０．０６３μｇ／ｍｌ，结果提示，ＡＤＭ－Ｄｅｘ－ＪＨ１１具有选择性细胞杀伤作用．

The conjugates, ADM Dex-JH11, of adriamycin (ADM) and monoclonal antibody JH11 (JH11) against liver cancer were prepared via the dextran btidge method.The molar ratio of ADM to JH11 in the conjugates was 71:1. By the indirect fluorescence assay, most actiyities of JH1, in the conjugates were reserved. In the cytotolicity test in vitro, the cytotoxicities of ADM-Dex-JH11 on liver cancer cell line BEL7402 were higher than that of free ADM; their IC50 were 0. 96μg/ml and 1. 52μg/ml,respectiyely. And the cytotoxicities of the conjugates on non-target cells MGc-803 and L342 were much weeker, with their IC50 being over 10μg/ml. At a low concentration,a remarkable inhibiting effect of ADM-Dex JH11 on the BEL-7402 was observed by the colony-forming assay, with its IC50 being 0. 063μg/ml. The results showed that JH11, had targeting activities and could kill or damage tumor cells by binding with adriamycin.