9B76

Crystal structure of humanized 44H10 Fab Version 21

Summary for 9B76

• Entry DOI: 10.2210/pdb9b76/pdb
• Descriptor: h44H10-V21 Antibody, heavy chain, h44H10-V21 Antibody, light chain, POTASSIUM ION, ... (5 entities in total)
• Functional Keywords: antibody, humanized, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 47662.11

Authors

Kassardjian, A.,Julien, J.P. (deposition date: 2024-03-27, release date: 2024-08-07, Last modification date: 2024-10-16)

Primary citation

Kassardjian, A.,Ivanochko, D.,Barber, B.,Jetha, A.,Julien, J.P.
Humanization of Pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework.
Antibodies, 13:-, 2024

PubMed 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 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.

PubMed: 39051333
DOI: 10.3390/antib13030057

Experimental method

X-RAY DIFFRACTION (1.73 Å)