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目的 研究人鼠嵌合抗体D2C的体外抗瘤活性和体内分布。方法 以表达CD71分子的人类肿瘤细胞(K562,CEM和SMMC-7721)为靶细胞,以新鲜分离的正常人外周血单个核细胞(PBMC)为效应细胞,在效/靶细胞比为50:1的条件下,用乳酸脱氢酶释放法测定嵌合抗体依赖性细胞介导的细胞毒效应(ADCC);以CEM和SMMC-7721为靶细胞,测定嵌合抗体的补体依赖性细胞毒效应(CDC);利用人肝癌细胞株(SMMC-7721)移植动物模型(Balb/c,nu/nu裸鼠),测定~(131)I标记嵌合抗体(~(131)I-D2C)体内抗体定位和分布。结果 嵌合抗体在体外介导的ADCC随着抗体浓度的增加而增强。在新鲜补体存在下,嵌合抗体对表达CD71分子的肿瘤细胞具有CDC。体内实验表明,全身或肿瘤局部使用嵌合抗体,在肿瘤组织局部均有特异性浓聚现象,局部使用抗体时,其对体内其他组织的非特异性分布低于全身使用时。结论 CD71人鼠嵌合抗体在体外对阳性肿瘤细胞有明显的杀伤作用,在体内模型中能特异地识别肿瘤组织并与之结合。
Objective To study the in vitro antitumor activity and in vivo distribution of human chimeric antibody D2C. Methods Using human tumor cell lines expressing CD71 (K562, CEM and SMMC-7721) as target cells and freshly isolated normal human peripheral blood mononuclear cells (PBMCs) as effector cells at a ratio of effective / target cells of 50: 1 , Chimeric antibody-dependent cell-mediated cytotoxicity (ADCC) was measured by lactate dehydrogenase release assay. The complement-dependent cytotoxic effect of chimeric antibody was measured using CEM and SMMC-7721 as target cells CDC). The in vivo antibody localization of ~ (131) I-labeled chimeric antibody (~ (131) I-D2C) was measured using an animal model of human hepatocellular carcinoma cell line SMMC-7721 transplanted in Balb / c mice And distribution. Results Chimeric antibodies mediated in vitro ADCC increased with increasing antibody concentration. Chimeric antibodies have CDC on tumor cells that express CD71 molecules in the presence of fresh complement. In vivo experiments show that systemic or tumor local use of chimeric antibodies, tumor tissue in the local have a specific concentration phenomenon, the topical use of antibodies, its non-specific distribution of other tissues in vivo is lower than when the body. Conclusion CD71 human chimeric antibody has obvious cytotoxicity on positive tumor cells in vitro, and can specifically identify tumor tissue and bind with it in in vivo model.