Antigen-Specific Immunomodulation in Multiple Sclerosis by IL-10 -T Cell Receptor-Like Antibodies Fusion Proteins

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) leading to demyelination and progressive neurologic disability. The development of MS is influenced by environmental factors and has a strong genetic association to the MHC class II allele, HLA-DR2 (DRB1*1501).

In the past 20 years, several immunotherapies, which target the peripheral immune system, have been approved for the treatment of MS, but none of these treatments are antigen specific. Besides, these treatments are particularly effective during the early phase of MS for reducing relapse rates and disability Progression, but they have little or no effect during the progressive phase which targeted by a local innate immune response.

Previous work in our laboratory identified TCR-like antibodies (TCRL Abs) that bind to the myelin peptide MOG35-55 in context with HLA-DR2.

Interleukin-10 (IL-10) is a strong anti-inflammatory cytokine directed mainly against the innate arm and suppress the immune response by inhibit the release of pro-inflammatory mediators and decrease antigen presentation and phagocytosis.

The goal of this study is to construct, produce, and characterize an IL-10 TCRL Ab fusion protein directed against the HLA-DR2/MOG35-55 complex and test its ability to modulate MS pathology. The major goal in this approach is to demonstrate a shift in the balance of the cytokines micro-environment toward an anti-inflammatory state indicating that the immunocytokine can induce antigen and sites specific immunomodulation, and will thus minimize the progressive MS pathology.