ADCC增强型Claudin18.2单克隆抗体的制备和体内外活性  

Preparation and in vitro and in vivo Activity of ADCC Enhanced Claudin18.2 Monoclonal Antibody

作　　者：朱中松 彭伟 刘忠 张贵民 赵丽丽 ZHU Zhongsong;PENG Wei;IU Zhong;ZHANG Guimin;ZHAO Li(Lunan New Time Bio-tech Co.,Ltd.,Linyi 273400;State Engineering Lab.of High Expression of Mammalian Cells,Linyi 273400;Lunan Pharmaceutical Group Co.,Ltd.,Linyi 276000)

机构地区：[1]鲁南新时代生物技术有限公司,山东临沂273400 [2]哺乳动物细胞高效表达国家工程实验室,山东临沂273400 [3]鲁南制药集团股份有限公司,山东临沂276000

出　　处：《中国医药工业杂志》2025年第2期190-197,共8页Chinese Journal of Pharmaceuticals

基　　金：泰山产业领军人才工程项目(tscx202306088)。

摘　　要：Claudin18.2抗体在胃癌治疗中具有巨大的潜力。然而,受限于其非人源序列和较弱的受体亲和力,已上市抗体的疗效和安全性仍有待改善。该研究通过杂交瘤筛选、抗体人源化和抗体依赖性细胞毒性(ADCC)作用的改造,获得了特异性结合Claudin18.2的单克隆抗体110E2A4-M2。随后,测定了抗体的ADCC和补体依赖性细胞毒性(CDC)活性,并在小鼠移植瘤模型中研究了其药效。结果显示,抗体110E2A4-M2的ADCC活性显著高于对照抗体IMAB362,且CDC活性未降低,在小鼠皮下移植瘤模型中表现出较强的抑瘤能力,肿瘤生长抑制率为52.35%。该研究为Claudin18.2抗体的开发提供了数据支持。The Claudin18.2 antibody holds significant potential in the treatment of gastric carcinoma.However,due to its non-human sequence and relatively weak receptor affinity,the efficacy and safety of the marketed antibodies still need to be improved.Through hybridoma screening,antibody humanization and modification of antibody-dependent cell-mediated cytotoxicity(ADCC),this study obtained the monoclonal antibody,named 110E2A4-M2,that specifically binds to Claudin18.2.Subsequently,the ADCC and complement-dependent cytotoxicity(CDC)activities of the antibody were determined,and its pharmacological effects were studied in a mouse xenograft tumor model.The results showed that the ADCC activity of 110E2A4-M2 was significantly higher than that of the control antibody(IMAB362),and its CDCactivity was not reduced.It displayed a relatively strong tumor-suppressing ability in the mouse subcutaneous xenografttumor model,with a tumor growth inhibition rate of 52.35%.This study provided data support for the development of Claudin18.2 antibodies.

关 键 词：胃癌 Claudin18.2单克隆抗体 杂交瘤技术 抗体人源化 抗体依赖性细胞毒性 基因工程 

分 类 号：R392-33[医药卫生—免疫学]