抗人CD40单克隆抗体的筛选及其人源化抗体的抗肿瘤活性评价  

Screening of Monoclonal Antibodies against Human CD40 and Antitumor Activity Evaluation of Humanized Antibodies

作　　者：赵丽丽 张晓丽 赵文鹏 朱中松 刘忠 ZHAO Lili;ZHANG Xiaoli;ZHAO Wenpeng;ZHU Zhongsong;LIU Zhong(Lunan New Time Bio-tech Co.,Ltd.,Linyi 273400;State Engineering Lab.of High Expression of Mammalian Cells,Linyi 273400;Shenyang Pharmaceutical University,Shenyang 110016;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]沈阳药科大学,辽宁沈阳110016 [4]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》2024年第1期58-65,共8页Chinese Journal of Pharmaceuticals

基　　金：泰山产业领军人才工程项目(tscy20200329、tscx202306088)。

摘　　要：CD40激动型抗体在治疗恶性肿瘤方面具有巨大的潜力,但其疗效和安全性仍有欠缺。该研究通过杂交瘤技术筛选到2株高结合力、高亲和力的激动型抗CD40单克隆抗体(31A2-2、42D11-8),对其进行人源化改造,并采用NPG小鼠移植瘤模型研究其药效。结果显示,改造后的抗体经测定仍具有较高的结合力和亲和力,在树突状细胞激活试验中显示出较强的激活能力,可刺激树突状细胞激活并释放IL-12。2株抗体在NPG小鼠体内均具有显著的抗肿瘤效果,肿瘤生长抑制率分别达到86.83%、87.95%。该研究为CD40激动型药物的开发提供了数据支持。Agonistic CD40 antibodies hold great potentials in the treatment of malignant tumors,yet their efficacy and safety remain to be fully established.This research identified and humanized two high-binding and high-affinity agonistic anti-CD40 monoclonal antibodies(31A2-2 and 42D11-8)via hybridoma technique,and evaluated their pharmacodynamics through the NPG mouse xenograft model.The results revealed that the modified antibodies maintained high binding affinity after measurement,and demonstrated robust activation capacity in dendritic cell activation assays,thereby stimulated dendritic cells to release IL-12.Both antibodies exhibited significant antitumor activities in NPG mice,with tumor growth inhibition rates reaching 86.83%and 87.95%respectively.This study provided data support for the development of agonistic CD40 drugs.

关 键 词：CD40单克隆抗体 杂交瘤技术 人源化抗体 抗肿瘤活性 

分 类 号：R979.19[医药卫生—药品] Q511[医药卫生—药学]