Specificity tuning of antibody fragments to neutralize two human chemokines with a single agent

被引：17

作者：

Fagete, Severine ^{[1
]}

Ravn, Ulla ^{[1
]}

Gueneau, Franck ^{[1
]}

Magistrelli, Giovanni ^{[1
]}

Kosco-Vilbois, Marie H. ^{[1
]}

Fischer, Nicolas ^{[1
]}

机构：

[1] NovImmune SA, CH-1228 Plan Les Ouates, Switzerland

来源：

MABS | 2009年 / 1卷 / 03期

关键词：

cross-reactive antibody; antibody arrays; chemotaxis; multiple targeting; affinity maturation; phage display; ANTIGEN INTERACTIONS; MOLECULAR EVOLUTION; CROSS-REACTIVITY; RECEPTOR CXCR3; INHIBITION; CELLS; CHEMOATTRACTANT; INFLAMMATION; RECRUITMENT; BLOCKADE;

D O I：

10.4161/mabs.1.3.8527

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Chemokines are important mediators of the immune response that are responsible for the trafficking of immune cells between lymphoid organs and migration towards sites of inflammation. Using phage display selection and a functional screening approach, we have isolated a panel of single-chain fragment variable (scFv) capable of neutralizing the activity of the human chemokine CXCL10 (hCXCL10). One of the isolated scFv was weakly cross-reactive against another human chemokine CXCL9, but was unable to block its biological activity. We diversified the complementarity determining region 3 (CDR3) of the light chain variable domain (VL) of this scFv and combined phage display with high throughput antibody array screening to identify variants capable of neutralizing both chemokines. Using this approach it is therefore possible to engineer pan-specific antibodies that could prove very useful to antagonize redundant signaling pathways such as the chemokine signaling network.

引用

页码：288 / 296

页数：9

共 28 条

[1] Chemokine: Receptor structure, interactions, and antagonism [J].