Humanization of Pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework.

ABSTRACT: Reducing the immunogenicity of animal-derived monoclonal antibodies (mAbs) for use in humans is critical to maximize therapeutic effectiveness and preclude potential adverse events. While traditional humanization methods have primarily focused on grafting antibody Complementarity-Determining Regions (CDRs) on homologous human antibody scaffolds, framework regions can also play essential roles in antigen binding. Here, we describe the humanization of the pan-HLA-DR mAb 44H10, a murine antibody displaying significant involvement of the framework region in antigen binding. Using a structure-guided approach, we identify and restore framework residues that directly interact with the antigen or indirectly modulate antigen binding by shaping the antibody paratope and engineer a humanized antibody

SUBMITTER: Kassardjian A 

PROVIDER: S-EPMC11270187 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature