抗人B7-1人-鼠嵌合抗体体内外抑瘤作用研究  

Inhibitory action of human-mouse chimeric antibody against B7-1 on tumor cell in vivo and in vitro

作　　者：王艳茹[1] 邱玉华[2] 

机构地区：[1]包头医学院护理学院,014060 [2]苏州大学医学部免疫学系,215123

出　　处：《免疫学杂志》2015年第9期753-756,共4页Immunological Journal

基　　金：江苏省高校高新技术产业发展基金(JHB05-45);江苏省自然科学基金(BK2004203)

摘　　要：目的研究抗人B7-1人-鼠嵌合抗体ch-4E5对高表达B7-1分子的人恶性B淋巴瘤细胞株Raji的抑瘤作用。方法自行制备ch-4E5,经流式细胞术(FCM)分析ch-4E5对Raji细胞膜型B7-1分子的识别及共育后细胞表面Fas及Fas L表达的改变,继而又经MTT法检测细胞增殖的抑制效应;以人外周血PBMC为效应细胞,Raji为靶细胞,分析ch-4E5介导的抗体依赖的细胞介导的细胞毒作用(antibody dependent cell mediated cytotoxicity,ADCC);将Raji细胞经ch-4E5处理后接种Balb/c裸鼠,观察裸鼠成瘤时间并计算成瘤率。结果 ch-4E5与Raji细胞的阳性结合率为97.9%;该抗体可上调Raji表面Fas及Fas L的表达,其阳性表达率分别为15.8%及16.9%,与人Ig G1同型对照组5.1%和2.2%比较具有统计学意义(P<0.01);ch-4E5对Raji细胞增殖的抑制率为39.17%(P<0.01);介导的最大杀伤率为56.47%(P<0.01);经ch-4E5处理的Raji细胞接种Balb/c裸鼠,90 d的观察期内均未见肿瘤形成,而对照组成瘤率高达80%。结论抗人B7-1人-鼠嵌合抗体对高表达B7-1的肿瘤细胞具有抑瘤作用。Raji cell, highly expresses B7-1 molecule, is a malignant B lymphoma cell line. The signal mediated by B7-1 is closely related to tumor proliferation and metastasis. On the basis of a human-mouse chimeric antibody against B7-1, named ch-4E5, constructed by our group, this study designed to analyze the recognition of ch-4E5 to membrane B7-1 in Raji and determine the expressions of Fas and FasL after the co-culture of ch-4E5 with Raji by flow cytometry, for evaluating the blocking effect on cell growth of ch-4E5. MTr assay was used to study the antibody dependent cell mediated cytotoxicity （ADCC）, with PBMC as effector cells and Raji as target cells. Raji cells treated by ch-4E5 were inoculated into Balb/c nude mouse to observe the formative time of tumor and calculate the formative rate of tumor. Data showed that the combination rate between ch-4E5 and Raji was 97.9%. After the co-culture of ch-4E5 with Raji, the positive expression rates of Fas and FasL on Raji cell surface were up-regulated to 15.8% and 16.9%, which were increased obviously （P〈 0.01）, as compared with human IgG1 control group （5.1% and 2.2%）; the inhibitory rate of ch-4E5 to Raji cell was 39.17% （P〈 0.01）. Furthermore, ch- 4E5 could mediate the ADCC and the maximum killing rate was 56.47% （P 〈 0.01）. After injection of ch-dE5 antibody-treated Raji cells, tumor was not seen in Balb/c nude mouse in 90 days, while the formative rate of tumor was 80% in the control group. Our results indicate that the human-mouse chimeric antibody against B7-1 has inhibitory action on tumor cells highly expressing B7-1 molecule.

关 键 词：B7-1 嵌合抗体 B淋巴瘤 抗体依赖的细胞介导的细胞毒作用 抑制作用 

分 类 号：R730.3[医药卫生—肿瘤]