cd276治疗性抗体对脑胶质瘤的研究
首发时间:2024-07-11
摘要:目的:针对cd276阳性的脑胶质瘤开发一种人源化fc段突变的重组抗体,体外评估抗体的有效性;体内评估抗体抑制脑胶质瘤的疗效。方法:将人源化cd276 抗体fc段糖基化位点f243l/r292p/y300l/v305i/p396l突变,获得的序列以基因合成的方式导入cho细胞,收集细胞上清后纯化;在jurkat-nfat-luciferase-cd16平台中通过荧光素酶表达水平验证其有效性;在人源化小鼠中通过外周血单核细胞(peripheral blood mononuclear cell,pbmc)重建nk细胞,体内验证其对脑胶质瘤u-87 mg的抑制作用。3.结果:成功将fc糖基化位点突变后获得两株人源化抗体:cd276t1h1l1-fc mut和cd276t2h1l1-fc mut抗体;在jurkat-nfat-luciferase-cd16平台中,对比未突变抗体,fc突变后抗体的adcc效应显著提高;在pbmc人源化小鼠内,cd276t1h1l1-fc mut组以剂量依赖的方式展现出良好的抗肿瘤效应。结论:fc突变的cd276重组抗体在体外具有良好的adcc效应(antibody-dependent cell-mediated cytotoxicity);在人源化小鼠模型中,fc突变的cd276重组抗体展现出良好的抗肿瘤效应。
关键词:
for information in english, please click here
the study of cd276 therapeutic antibody on glioma
abstract:to develop a humanized fc segment mutant recombinant antibody targeting cd276 positive gliomas and further evaluate its efficacy in vitro; evaluate the inhibitory effect of this antibody on glioma in vivo. method: the fc glycosylation site f243l/r292p/y300l/v305i/p396l of humanized cd276 antibody was mutated, and the obtained sequence was introduced into cho cells through gene synthesis. the cell supernatant was collected and purified; validate its effectiveness through luciferase expression levels in the jurkat-nfat-luciferase-cd16 platform; reconstruct nk cells through peripheral blood mononuclear cells (pbmcs) in humanized mice and validate their inhibitory effect on u-87 mg glioma in vivo. 3. result: two humanized antibodies were obtained after successfully mutating the fc glycosylation site: cd276t1h1l1 fc mut and cd276t2h1l1 fc mut antibodies; in the jurkat-nfat luciferase cd16fc platform, the adcc effect of fc mutated antibodies was significantly increased compared to unmodified antibodies; in pbmc humanized mice, the cd276t1h1l1 fc mut group exhibited good anti-tumor effects in a dose-dependent manner. conclusion: the cd276 recombinant antibody with fc mutation has good efficacy in vitro; in humanized mouse models, the cd276 recombinant antibody with fc mutation showed good anti-tumor effects.
keywords:
基金:
论文图表:
引用
导出参考文献
no.****
动态公开评议
共计0人参与
勘误表
cd276治疗性抗体对脑胶质瘤的研究
评论
全部评论