A LAG-3-Specific Agonist Antibody for the Treatment of T Cell-Induced Autoimmune Diseases

Abstract

T cells chronically stimulated with the same peptide tend to express exhaustion markers such as PD-1 or LAG-3. Deficiencies in the PD-1 and LAG-3 pathways have been linked to the development of autoimmune diseases. IMP761 is a LAG-3-specific humanized agonist Ab with immunosuppressive properties both in vitro and in vivo in an Ag-specific delayed-type hypersensitivity (DTH) model in the cynomolgus macaque (Macaca fascicularis). IMP761 inhibits TCR-mediated NFAT activation and Ag-induced human T cell proliferation and activation. In the DTH model, assessment of T cell infiltration and gene expression profile at the DTH biopsy site corresponds to immunosuppression of an Ag-induced T cell response. IMP761 is the first LAG-3-specific agonist product candidate, acting upstream on activated T cells, the root cause of self-Ag-specific T cell-induced autoimmune diseases.