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Chapitre D'ouvrage Année : 2019

Antibody Fragments Humanization: Beginning with the End in Mind

Nicolas Aubrey
Philippe Billiald
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Résumé

Molecular engineering has made possible to reformat monoclonal antibodies into smaller antigen-binding structures like scFvs, diabodies, Fabs with new potential in vivo applications because they do not induce Fc-mediated functions. However, most of these molecules are from rodent origin. As a consequence, they are immunogenic and approval for administration to humans requires prior humanization. Today, there is no well-identified strategy to create recombinant humanized antibody V-domains that preserve the antigen-binding characteristics of the parental antibody associated with high stability and solubility. Here, we propose a strategy that consists in grafting CDRs onto properly chosen human antibody frameworks in order to reduce immunogenicity. A flowchart indicates the way to proceed in order to introduce an internal affinity purification tag while structural refinements are proposed to maintain antigen-binding characteristics. The best humanized candidates are identified through selection steps including in silico analysis, research scale production followed by early functional evaluation, purification assays, aggregation, and stability assessment.
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Dates et versions

hal-02789902 , version 1 (05-06-2020)

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Citer

Nicolas Aubrey, Philippe Billiald. Antibody Fragments Humanization: Beginning with the End in Mind. Human Monoclonal Antibodies : Methods and Protocols, 1904 (2ème ed.), Humana Press, 2019, Methods in Molecular Biology, 978-1-4939-8957-7. ⟨10.1007/978-1-4939-8958-4_10⟩. ⟨hal-02789902⟩
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