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Developing Antigen-Specific Therapies for Systemic Lupus Erythematosus

Posted January 3, 2023

Joshua Ooi, Ph.D., Monash University

Dr. Joshua Ooi, Monash University Dr. Joshua Ooi
(Photo provided)

Dr. Joshua Ooi, Monash University, received an award from the Congressionally Directed Medical Research Programs’ Lupus Research Program titled, “Targeted Regulatory T Cells to Treat Systemic Lupus Erythematosus.” The purpose of the project is to develop a cell-based therapy to inhibit the inflammatory immune response against lupus antigens, in particular, the Smith (Sm) antigen. Autoreactivity against the Sm lupus antigen is associated with severe disease and, particularly, severe lupus nephritis.

Dr. Joshua Ooi, Monash University

In prior work, the principal investigator developed improved methods to isolate and identify human leukocyte antigen (HLA)-associated peptides and developed T-cell receptor clones with enhanced reactivity with the HLA-peptide complexes, and also generated autoantigen-specific targeted regulatory T cells (Tregs). Additional work established a humanized mouse model of lupus nephritis using patient blood to test the efficiency of the newly generated targeted Tregs in suppressing human pathogenic autoimmune responses. The Tregs proved to be more effective than unmodified Tregs in their humanized mouse model.

The aims of the current award are to (1) use Sm-specific regulatory T cells (Sm-Tregs) to suppress the autoimmunity of SLE, (2) determine the long-term in vivo persistence and stability of Sm-Tregs (using their humanized animal model), and (3) identify different SLE autoantigens on patients’ harvested dendritic cells. The project will continue development of their methodology using SLE patient-derived Tregs to treat autoimmunity in a mouse model of SLE.

If successful, one of the main outcomes of the award will be the ability to affect only the proinflammatory T cells and B cells relevant to SLE treatment instead of suppression of the entire immune system, with the deleterious effects attendant on suppressing the entire immune system.


Links:
Public and Technical Abstracts: Targeted Regulatory T Cells to Treat SLE

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Last updated Thursday, December 5, 2024