Fagète Séverine, Ravn Ulla, Gueneau Franck, Magistrelli Giovanni, Kosco-Vilbois Marie H, Fischer Nicolas
NovImmune SA, Plan-les-Ouates, Switzerland.
MAbs. 2009 May-Jun;1(3):288-96. doi: 10.4161/mabs.1.3.8527.
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.
趋化因子是免疫反应的重要介质，负责免疫细胞在淋巴器官之间的运输以及向炎症部位的迁移。通过噬菌体展示筛选和功能筛选方法，我们分离出了一组能够中和人趋化因子CXCL10（hCXCL10）活性的单链可变片段（scFv）。分离出的一种scFv与另一种人趋化因子CXCL9有弱交叉反应，但无法阻断其生物活性。我们对该scFv轻链可变区（VL）的互补决定区3（CDR3）进行多样化改造，并将噬菌体展示与高通量抗体阵列筛选相结合，以鉴定能够中和这两种趋化因子的变体。因此，使用这种方法可以设计出泛特异性抗体，这可能对拮抗冗余信号通路（如趋化因子信号网络）非常有用。
