Version 1
: Received: 21 May 2024 / Approved: 21 May 2024 / Online: 22 May 2024 (14:46:25 CEST)
How to cite:
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. Preprints2024, 2024051417. https://doi.org/10.20944/preprints202405.1417.v1
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. Preprints 2024, 2024051417. https://doi.org/10.20944/preprints202405.1417.v1
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. Preprints2024, 2024051417. https://doi.org/10.20944/preprints202405.1417.v1
APA Style
Kassardjian, A., Ivanochko, D., Barber, B., Jetha, A., & Julien, J. P. (2024). Humanization of pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework. Preprints. https://doi.org/10.20944/preprints202405.1417.v1
Chicago/Turabian Style
Kassardjian, A., Arif Jetha and Jean-Philippe Julien. 2024 "Humanization of pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework" Preprints. https://doi.org/10.20944/preprints202405.1417.v1
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.
Keywords
antibody humanization; framework regions; vernier zone; MHC class II targeting
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
