title: Humanization of an anti-ICAM-1 antibody with over 50-fold affinity and functional improvement.
abstract: 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.
authors.affiliation: Perlan Therapeutics Inc., 6310 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Guang X
authors.initials: GX
authors.lastname: Luo
authors.forename: Lori A
authors.initials: LA
authors.lastname: Kohlstaedt
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Charles
authors.forename: Elliott
authors.initials: E
authors.lastname: Gorfain
authors.forename: Ianessa
authors.initials: I
authors.lastname: Morantte
authors.forename: Jimmy H
authors.initials: JH
authors.lastname: Williams
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D022801:Complementarity Determining Regions; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1