一种适用于评价CD20抗体体内外抗肿瘤效应模型的建立  

Establishment of a novel model suitable to evaluate the antitumor activity of anti-CD20 antibodies

作　　者：刘广洛[1] 钱卫珠[2] 李博华[2] 杨扬[2] 许静[2] 王皓[2] 

机构地区：[1]解放军150医院胸心外科,洛阳471031 [2]第二军医大学肿瘤研究所,上海抗体药物国家工程研究中心,上海200433

出　　处：《现代免疫学》2010年第4期293-297,共5页Current Immunology

摘　　要：研究通过基因转染的方法建立了稳定表达不同水平人CD20分子的小鼠骨髓瘤细胞克隆:CD20高表达(NS1-CD20H)、中表达(NS1-CD20M)和低表达(NS1-CD20L)的NS-1细胞株。利用建立的CD20分子高、中、低表达的NS-1细胞系,我们初步研究了CD20分子表达水平与CD20抗体杀伤活性的关系。实验结果表明,随着CD20分子表达水平的提高,CD20抗体(Rituximab和2F2)的CDC和ADCC作用均相应增强。2F2抗体具有与Rituximab相似的ADCC作用。对于CD20高表达细胞,2F2抗体显示出和Rituximab相似的CDC活性。但对于CD20低表达的NS-1细胞,2F2的CDC活性远强于Rituximab。体内实验结果表明对于荷有NS1-CD20L的小鼠,Rituximab不能显示出抗肿瘤活性,而2F2则具有显著的抗肿瘤作用。由于这两个抗体有相似的ADCC活性,实验结果提示CDC可能是CD20抗体的重要作用机制之一。我们建立的不同程度表达CD20的NS-1细胞克隆可以成为一种新型的CD20抗体活性评价模型,并有助于进一步阐明CD20抗体的作用机制。In the present study,the mouse NS-1 rnyeloma cell lines stably expressing different levels of human CD20 molecule were firstly established by gene transfection techniques：i.e.NS1-CD20H （high level）,NS1-CD20M （middle level） and NS1-CD20L （low level）,and then the relationship between the CD20 expression level and the killing activity of CD20 antibodies were investigated. Our data showed that CD20 antibodies （Rituximab and 2F2） could mediate more potent complement-dependent cytotoxicity （CDC） or antibody-dependent cellular cytotoxicity （ADCC） in NS-1 cell lines expressing higher levels of human CD20 molecule. Rituximab and 2F2 were equally effective in mediating ADCC. Rituximab also showed similar CDC activity as 2F2 in NS-1 cell lines expressing high levels of human CD20. However,the CDC activity of 2F2 was significantly more potent than that of rituximab in NS1-CD20L cell lines. Immunotherapeutic studies further demonstrated that 2F2 was effective in prolonging the survival time of mice bearing NS1-CD20L tumor but rituximab was not. Because 2F2 displayed a similar ability to mediate ADCC compared with rituximab,it could be concluded that CDC might be one of critical mechanisms of action of CD20 antibodies. The NS-1 cell lines expressing different levels of human CD20 molecules established in this study may be a novel model for evaluating the anti-CD20 antibodies and help to elucidate their mechanisms of action.

关 键 词：CD20 RITUXIMAB 单克隆抗体 B细胞非霍奇金淋巴瘤 

分 类 号：R392.12[医药卫生—免疫学]