9b76

Publication Abstract from PubMed

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 with affinity, biophysical profile, and molecular binding basis comparable to that of the parental 44H10 mAb. As a humanized molecule, this antibody holds promise as a scaffold for the development of MHC class II-targeting therapeutics and vaccines.

Humanization of Pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework.,Kassardjian A, Ivanochko D, Barber B, Jetha A, Julien JP Antibodies (Basel). 2024 Jul 16;13(3):57. doi: 10.3390/antib13030057. PMID:39051333^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.