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

IF 4.5 3区 医学 Q2 IMMUNOLOGY European Journal of Immunology Pub Date : 2024-12-20 DOI:10.1002/eji.202451264
Victoria Daventure, Melissa Bou-Jaoudeh, Emna Hannachi, Alejandra Reyes-Ruiz, Amélia Trecco, Sandrine Delignat, Sébastien Lacroix-Desmazes, Claire Deligne
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Abstract

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-Fcdiv) or a monovalent heterodimer (IdeS-Fcmonov), 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-Fcmonov 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.

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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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