Humanization of an anti-ICAM-1 antibody with over 50-fold affinity and functional improvement.
The monoclonal antibody 1A6 binds to human intercellular adhesion molecule 1 (ICAM-1, CD54) and inhibits infection by 90% of human rhinovirus (HRV) serotypes. To make a therapeutic molecule for preventing and treating HRV infection, we humanized a single chain antibody (scFv), 1A6, by a structure-guided complementarity-determining region (CDR) grafting procedure. Our final humanized 1A6 scFv does not retain any mouse back mutations in the framework. Without changing the CDR sequences, the humanized 1A6 scFv demonstrates over 50-fold improvement in both affinity for ICAM-1 and protection efficacy against HRV infection in vitro.
Luo
Guang X
GX
Perlan Therapeutics Inc., 6310 Nancy Ridge Drive, San Diego, CA 92121, USA.
Kohlstaedt
Lori A
LA
Charles
Catherine H
CH
Gorfain
Elliott
E
Morantte
Ianessa
I
Williams
Jimmy H
JH
Fang
Fang
F
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000915:Antibody Affinity; D022801:Complementarity Determining Regions; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010850:Picornaviridae Infections / Q000517:prevention & control / Q000628:therapy / Q000821:virology; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D012229:Rhinovirus / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D022801:Complementarity Determining Regions; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1