An effective strategy for the humanization of antibody fragments under an accelerated timeline - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles International Journal of Biological Macromolecules Year : 2022

An effective strategy for the humanization of antibody fragments under an accelerated timeline

Abstract

The use of monoclonal antibodies (mAbs) in therapy is gradually advancing and discussions entail its safety, rentability and effectiveness. To this date, around a hundred mAbs have been approved by the FDA for the treatment of various diseases. Aiming for their large-scale production, recombinant DNA technology is mainly employed, and antibodies can be expressed in various eukaryotic and prokaryotic systems. Moreover, considering their heterologous origin and potential immunogenicity, various strategies have been developed for mAb humanization, considering that around 50 % of commercial mAbs are humanized. Hence, we introduce LimAb7, a mouse mAb capable of binding and neutralizing brown spider's Loxosceles intermedia dermonecrotic toxins in vivo/in vitro. This antibody has been produced in mouse and humanized scFv and diabody formats, however results indicated losses in antigen-binding affinity, stability, and neutralizing ability. Intending to develop evolved, stable, and neutralizing antibody fragments, we report for the first time the design of humanized antibody V-domains produced as Fab fragments, against spider venom toxins. Improvements in constructs were observed regarding their physicochemical stability, target binding and binding pattern maintenance. As their neutralizing features remain to be characterized, we believe this data sheds new light on antibody humanization by producing a parental molecule in different recombinant formats.
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Dates and versions

hal-03737814 , version 1 (25-07-2022)

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Isabella Gizzi Jiacomini, Martina Beltramino, Fanny Boursin, João Carlos Minozzo, Juliana Ferreira de Moura, et al.. An effective strategy for the humanization of antibody fragments under an accelerated timeline. International Journal of Biological Macromolecules, 2022, 216, pp.465-474. ⟨10.1016/j.ijbiomac.2022.06.195⟩. ⟨hal-03737814⟩
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