Design, construction, and in vitro analyses of multivalent antibodies
Design, construction, and in vitro analyses of multivalent antibodies
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DOI：
10.4049/jimmunol.170.9.4854
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发表时间：
2003-05-01
影响因子：
4.4
通讯作者：
Presta, L
中科院分区：
文献类型：
--
作者：
Miller, K;Meng, G;Presta, L
一些Ab在交联形成二聚体或多聚体后更有效，推测是由于结合并聚集更多表面靶标以扩增或多样化细胞信号传导。为了提高这些类型的抗体的治疗效力，我们设计并产生了表达串联Fab重复序列的抗体，目的是模拟交联的抗体。该系统的通用设计使得能够产生一系列多价人IgG Ab形式，包括四价IgG 1、四价F（ab '）（2）和具有三个或四个连续连接的Fab的线性Fab多聚体。多聚化的Ab靶向细胞表面受体HER2、死亡受体5和CD20，并且在触发抗肿瘤细胞应答方面比它们的亲本mAb更有效，表明它们可以用作研究试剂以及新型治疗剂。
Some Abs are more efficacious after being cross-linked to form dimers or multimers, presumably as a result of binding to and clustering more surface target to either amplify or diversify cellular signaling. To improve the therapeutic potency of these types of Abs, we designed and generated Abs that express tandem Fab repeats with the aim of mimicking cross-linked Abs. The versatile design of the system enables the creation of a series of multivalent human IgG Ab forms including tetravalent IgG1, tetravalent F(ab')(2), and linear Fab multimers with either three or four consecutively linked Fabs. The multimerized Abs target the cell surface receptors HER2, death receptor 5, and CD20, and are more efficacious than their parent mAbs in triggering antitumor cellular responses, indicating they could be useful both as reagents for study as well as novel therapeutics.