4.7 Article

An engineered Fc fusion protein that targets antigen-specific T cells and autoantibodies mitigates autoimmune disease

Journal

JOURNAL OF NEUROINFLAMMATION
Volume 20, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12974-023-02974-9

Keywords

Multiple sclerosis; EAE; Fc fusion; T cells; Autoantibodies; Tolerance; Myelin oligodendrocyte glycoprotein (MOG)

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Current therapies for autoimmune diseases mainly rely on immunomodulation of T and B cell responses. However, therapeutic removal of autoantibodies remains challenging. In this study, a fusion protein targeting both T cells and autoantibodies was developed and shown to efficiently clear autoantibodies and promote T cell tolerance, providing a therapeutically advantageous approach for autoimmunity.
Current effective therapies for autoimmune diseases rely on systemic immunomodulation that broadly affects all T and/or B cell responses. An ideal therapeutic approach would combine autoantigen-specific targeting of both T and B cell effector functions, including efficient removal of pathogenic autoantibodies. Albeit multiple strategies to induce T cell tolerance in an autoantigen-specific manner have been proposed, therapeutic removal of autoantibodies remains a significant challenge. Here, we devised an approach to target both autoantigen-specific T cells and autoantibodies by producing a central nervous system (CNS) autoantigen myelin oligodendrocyte glycoprotein (MOG)-Fc fusion protein. We demonstrate that MOG-Fc fusion protein has significantly higher bioavailability than monomeric MOG and is efficient in clearing anti-MOG autoantibodies from circulation. We also show that MOG-Fc promotes T cell tolerance and protects mice from MOG-induced autoimmune encephalomyelitis. This multipronged targeting approach may be therapeutically advantageous in the treatment of autoimmunity.

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