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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。
Objective To study the anti-tumor effect of anti-human B7-1 human-mouse chimeric antibody ch-4E5 on human malignant B lymphoma cell line Raji with high expression of B7-1. Methods The ch-4E5 cells were induced by ch-4E5, and the changes of cell surface Fas and Fas L expression were detected by flow cytometry (FCM). The cells were detected by MTT assay (PBMC) as the effector cells and Raji as the target cell, we analyzed the ch-4E5-mediated antibody dependent cell mediated cytotoxicity (ADCC) Balb / c nude mice were inoculated with ch-4E5 and the tumor formation time was counted and the tumor formation rate was calculated. Results The positive rate of binding of ch-4E5 to Raji cells was 97.9%. The antibody could up-regulate the expression of Fas and Fas L on Raji cells. The positive rate of expression was 15.8% and 16.9% (P <0.01); The inhibitory rate of ch-4E5 on Raji cell proliferation was 39.17% (P <0.01); the maximum killing rate was 56.47% (P <0.01) Balb / c nude mice were inoculated with 4E5-treated Raji cells for a median of 80% of the control in the 90-day observation period. Conclusion Anti-human B7-1 human-mouse chimeric antibody has anti-tumor effect on tumor cells highly expressing B7-1.