title: Humanization of antagonistic anti-human 4-1BB monoclonal antibody using a phage-displayed combinatorial library.
abstract: Anti-4-1BB (CD137) monoclonal antibody (mAb) has been reported to suppress immune responses and to have the potential for use as a therapeutic agent to block autoimmune diseases. Previously, the authors prepared an antagonistic anti-human 4-1BB (CD137) mAb, BBK2. Here the authors report the humanization of BBK2 using a phage display library. Four humanized single-chain Fv (scFv) fragments were selected from a combinatorial library expressing a phage-displayed humanized scFv. They were found to retain the epitope specificity of the original mAb and to have affinities higher than those of the original. Both the soluble and bound forms of the humanized scFv suppressed the proliferation of human peripheral blood mononuclear cells, similar to the original mAb. These results suggest that humanized anti-human 4-1BB scFvs can be used as a valuable reagent for clinical application.
authors.affiliation: Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan, Ulsan, Korea.
authors.forename: Unn Hwa
authors.initials: UH
authors.lastname: Lee
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Son
authors.forename: Jeong Jin
authors.initials: JJ
authors.lastname: Lee
authors.forename: Byungsuk
authors.initials: B
authors.lastname: Kwon
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Byoung
authors.initials: B
authors.lastname: Se Kwon
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D015703:Antigens, CD; D001667:Binding, Competitive; D002455:Cell Division; D002469:Cell Separation; D004247:DNA / Q000737:chemistry; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015723:Gene Library; D006801:Humans; D007128:Immunoglobulin Fragments; D007158:Immunologic Techniques; D007167:Immunotherapy; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008969:Molecular Sequence Data; D019151:Peptide Library; D011485:Protein Binding; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry*; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D007128:Immunoglobulin Fragments; D019151:Peptide Library; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D004247:DNA