抗CD3人源化抗体恒定区突变体的体外生物学特性研究  

Characterization of a humanized anti-CD3 antibody containing mutated constant region

作　　者：李博华[1] 王皓[1] 杨扬[1] 钱卫珠[1] 季军捷[1] 王荣福[1] 郭亚军[1] 

机构地区：[1]第二军医大学肿瘤研究所

出　　处：《中华微生物学和免疫学杂志》2003年第8期584-587,共4页Chinese Journal of Microbiology and Immunology

基　　金：上海市重大基础研究项目 (99JC14 0 46) ;国家自然科学基金资助项目 (3 0 0 2 5 0 3 9)

摘　　要：目的　研究抗CD3人源化抗体hu12F6的恒定区突变体hu12F6m的体外生物学活性。方法　通过细胞因子释放分析及早期活化标志分子的检测对hu12F6m的T细胞活化性质进行评价 ;通过体外抗原调变实验考察hu12F6m对T细胞的抑制功能。结果　hu12F6m激活T细胞释放TNF α、IFN γ、IL 10等细胞因子及表达早期活化标志CD6 9分子的水平明显低于hu12F6 ,但其调变CD3抗原的能力保持与hu12F6相似。结论　hu12F6m对T细胞的激活作用显著减弱并保留了对T细胞的抑制功能 ,有望成为一种抗排异能力强、免疫原性和毒副作用小的有效免疫抑制剂。Objective To study the in vitro biological activity of hu12F6m, a humanized anti-CD3 antibody (hu12F6) containing mutated Fc region. Methods T cell activation properties of hu12F6m were assessed by cytokine secretion and early activation marker expression; Immunosuppressive properties of hu12F6m were determined by in vitro TCR/CD3 modulation experiments. Results hu12F6m was much less potent in the induction of cytokine release (TNF-α, IFN-γ and IL-10) and early activation marker expression (CD69) than hu12F6. But hu12F6m had a similar ability to modulate the TCR/CD3 comparing with hu12F6. Conclusion hu12F6m had a marked reduction in the T cell activation but retained potent immunosuppressive properties. It might be an effective immunosuppressive agent with less immunogenicity and toxicity.

关 键 词：CD3 人源化抗体 免疫抑制剂 抗原调变 hul2F6m 

分 类 号：R392[医药卫生—免疫学]