Specificity tuning of antibody fragments to neutralize two human  chemokines with a single agent.
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.
Fagète
Séverine
S
NovImmune SA, Plan-les-Ouates, Switzerland.
Ravn
Ulla
U
Gueneau
Franck
F
Magistrelli
Giovanni
G
Kosco-Vilbois
Marie H
MH
Fischer
Nicolas
N
D019138:Antibodies, Blocking / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000915:Antibody Affinity; D054357:Chemokine CXCL10 / Q000276:immunology*; D054370:Chemokine CXCL9 / Q000276:immunology*; D020650:Combinatorial Chemistry Techniques; D022801:Complementarity Determining Regions / Q000737:chemistry; D003429:Cross Reactions; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D057166:High-Throughput Screening Assays; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry; D019151:Peptide Library; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
D019138:Antibodies, Blocking; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D022801:Complementarity Determining Regions; D000939:Epitopes; D007147:Immunoglobulin Light Chains; D019151:Peptide Library; D057127:Single-Chain Antibodies