Pharmaceuticals
Treatment of Autoimmune Diseases by Modulating Bregs (No. T4-1441)

5470
Summary

Autoimmune diseases, including type 1 diabetes, multiple sclerosis (MS), rheumatoid arthritis, lupus, and Crohn's disease, are characterized by the self-attack of the immune system. These conditions affect millions of people worldwide and their prevalence is increasing. Treatment is currently limited, and some diseases, such as MS, have no available cure. Therefore, there is an urgent need for new therapeutic approaches. Prof. Idit Shachar and her team identified a new regulator that controls the expression of regulatory B cells. They showed that blocking this protein using monoclonal antibodies limited excessive inflammation and reduced disease severity in an MS murine model, providing a novel treatment for autoimmune diseases.

Background and Unmet Need

Autoimmune diseases are characterized by the self-attack of the immune system on functional body cells. There are over 80 different autoimmune diseases, including type 1 diabetes, multiple sclerosis (MS), rheumatoid arthritis, lupus, Crohn's disease, psoriasis, and scleroderma. Although most of them are rare, they were estimated to affect approximately 3% of the world's population and represent the third most common cause of chronic illness in the United States. For unknown reasons, the prevalence of autoimmune diseases is increasing. 1

Regulatory B cells (Breg) are a subset of B cells that limit excessive inflammation (mainly via IL-10 production) and support immunological tolerance. Previous reports demonstrated the roles of Bregs in autoimmune diseases, including type 1 diabetes (T1D), rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD). However, the mechanisms regulating Breg abundance are poorly understood.

The Solution

Prof. Idit Shachar and her team identified SLAMF5 as a new regulator of Breg maintenance and function. They demonstrated in an MS mouse model that SLAMF5 blocking increased Breg survival and ameliorated disease severity.2

Technology's Essence

Crosstalk of B cells with their environment is crucial for their survival, activation, and differentiation. The SLAM (Signaling Lymphocytic Activating Molecules) family of immunomodulating receptors helps mediate the interaction of immune cells with their microenvironment. Prof. Idit Shachar and her team identified SLAMF5 (CD84) as a regulator of Breg maintenance and function. Using a murine model of MS known as experimental autoimmune encephalomyelitis (EAE), they demonstrated that deficiency of SLAMF5 in B cells induced accumulation of Bregs in the CNS and periphery. Blocking SLAMF5 in-vitro induced both human and murine IL-10 producing B cells (Bregs) and increased their survival with a concomitant increase of the transcription factor, c-Maf. Moreover, in-vivo blocking of SLAMF5 in EAE mice elevated Breg levels and ameliorated disease severity (Figure 1). Finally, the team showed that SLAMF5 expression is elevated in pro-inflammatory microglia in the EAE model. Therefore, SLAMF5 is a novel negative moderator of regulatory B cells and a potential target for MS treatment.

 

Applications and Advantages
  • Novel target that functions like Breg negative regulator
  • Extracellular marker for this unique population
  • The antibodies has completed the humanization process
Development Status

Shachar and her team identified SLAMF5 as a negative regulator of Breg cells' survival in mice and human cells. They demonstrated its role in a murine MS model and developed monoclonal antibodies, showing it could be used as a novel therapeutic target for MS. Finally, they showed that SLAMF5 is overexpressed in Breg cells from MS patients.

References
  1. Prevalence of Autoimmune Diseases - Autoimmune Disease | Johns Hopkins Pathology. Accessed January 17, 2022. https://pathology.jhu.edu/autoimmune/prevalence
  2. Radomir L, Kramer MP, Perpinial M, et al. The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5. Nat Commun. 2021;12(1):1893. doi:10.1038/s41467-021-22230-z
Patent Status: 
USA Granted: 10,611,839 USA Granted: 9,109,029 USA Granted: 10,329,347 USA Granted: 10,828,318 USA Granted: 8,686,121 USA Granted: 10,066,014
Full Professor Idit Shachar

Idit Shachar

Faculty of Biology
Department of Immunology
All projects (2)
Contact for more information

Dr. Yael Klionsky

Director of Business Development, Life Science

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