Half-Life Extension of the IgG-Degrading Enzyme (IdeS) Using Fc-Fusion Technology.

Autor: Daventure V; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, CNRS, Sorbonne Université, Université Paris Cité, Paris, France., Bou-Jaoudeh M; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, CNRS, Sorbonne Université, Université Paris Cité, Paris, France., Hannachi E; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, CNRS, Sorbonne Université, Université Paris Cité, Paris, France., Reyes-Ruiz A; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, CNRS, Sorbonne Université, Université Paris Cité, Paris, France., Trecco A; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, CNRS, Sorbonne Université, Université Paris Cité, Paris, France., Delignat S; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, CNRS, Sorbonne Université, Université Paris Cité, Paris, France., Lacroix-Desmazes S; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, CNRS, Sorbonne Université, Université Paris Cité, Paris, France., Deligne C; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, CNRS, Sorbonne Université, Université Paris Cité, Paris, France.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2024 Dec 20, pp. e202451264. Date of Electronic Publication: 2024 Dec 20.
DOI: 10.1002/eji.202451264
Abstrakt: Imlifidase (IdeS) is a bacterial protease that hydrolyzes human IgG in their hinge region, decreasing their half-life and abrogating their Fc-mediated properties. It is now successfully used in therapy to prevent graft rejection during kidney transplants and is being clinically evaluated in several IgG-mediated autoimmune diseases. IdeS short half-life however limits its clinical use, particularly in the case of chronic diseases that would request repeated administrations. Here, we developed IdeS-Fc fusion proteins as a divalent homodimer (IdeS-Fc div ) or a monovalent heterodimer (IdeS-Fc monov ), in order to extend the IgG-depleting action of IdeS over time. Both IdeS-Fc efficiently separated monoclonal and polyclonal human IgG into F(ab') 2 and Fc fragments, although with slower kinetics than their native counterpart. IdeS-Fc monov exhibited a seven-fold half-life extension in vivo as compared with IdeS, and a significantly better residual cleavage of human IgG at later time points after injection. Our results provide proof of concept for the use of an IdeS with extended IgG-hydrolyzing functions in vivo that could rapidly translate to the clinic.
(© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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