抗TIGIT单克隆抗体的制备及体外生物学活性的初步研究  

Preparation of anti-human TIGIT monoclonal antibody and preliminary study of its biological activity

作　　者：吴振华 李娜 陈娟 蒋美珠 陈瑶 梅小芬 王海彬 WU Zhen-hua;LI Na;CHEN Juan;JIANG Mei-zhu;CHEN Yao;MEI Xiao-fen;WANG Hai-bin(BioRay Pharmaceutical Co.,Ltd.,Taizhou 318000,China)

机构地区：[1]浙江博锐生物制药有限公司,浙江台州318000

出　　处：《药学学报》2022年第11期3310-3315,共6页Acta Pharmaceutica Sinica

摘　　要：T细胞免疫球蛋白和ITIM结构域蛋白(TIGIT)通过多种机制抑制固有和适应性免疫,是肿瘤免疫治疗的新型靶点。本研究利用重组人源TIGIT胞外区蛋白免疫BALB/c小鼠(本研究中的小鼠按照国际实验动物护理和使用准则进行使用,并经委托单位京天成生物技术(北京)有限公司实验动物伦理委员会批准),分离并提取小鼠脾淋巴细胞常规融合,成功筛选得到抗TIGIT单克隆抗体c7D3,并初步研究了其生物学活性。结果表明,抗体c7D3能高亲和地结合TIGIT,并能有效阻断TIGIT与配体的结合。细胞功能实验证实,c7D3能激活T细胞,在TIGIT/CD155报告基因实验中促进荧光素酶表达,提高人外周血单个核细胞分泌细胞因子的能力。本研究表明,抗体c7D3具有高亲和力和良好的生物学活性,有望开发成为新的肿瘤免疫治疗的抗体药物。T cell immune receptor with Ig and ITIM domains(TIGIT),a promising new target in cancer immunotherapy,plays a critical role in limiting adaptive and innate immunity against tumors.The extracellular domain of human TIGIT was used to immune BALB/c mice,and a new anti-human TIGIT chimeric antibody(c7D3)was developed.The mice in this study were used in accordance with the international guidelines for the care and use of laboratory animals,and the animal study was approved by the Institutional Animal Ethics Committee of AbMax Biotechnology.The biological activity of c7D3 was studied.The results showed that c7D3 exhibited high affinity for TIGIT and effectively inhibited the interaction between TIGIT and its ligands.Cell-based assays indicated that c7D3 induced strong luciferase signaling in TIGIT/CD155 signaling reporter assay and enhanced cytokine secretion in a T cell stimulation assay.The data showed that c7D3 has high binding affinity and excellent blocking bioactivity,supporting the further advancement for therapeutic application.

关 键 词：TIGIT 杂交瘤 单克隆抗体 嵌合抗体 生物学活性 

分 类 号：Q789[生物学—分子生物学]