Targeting the V-Type Immunoglobulin Domain-Containing Suppressor to T Cell Activation (VISTA) with Agonist Monoclonal Antibodies in Autoimmunity.

Abstract

The recognition of self-antigens by the T-cell immune system can results in autoimmunity. Current treatments of autoimmunity include non-steroid anti-inflammatory drugs and treatments aimed to control the immune system directly. Additionally, inhibiting signaling pathways that encourage T cell activation are promising strategies to help increase self-tolerance and control the inflammatory immune response. Despite the many treatments available, there are still great risks that accompanies each therapy; therefore, the shift towards immune checkpoint therapy is promising as it specifically targets the activated autoimmune T cells. In contrast to cancer, immune check point inhibitors (ICIs) for autoimmune treatment are attractive targets for the amplification of inhibitory functions of autoimmune T cells. A particular protein of interest for autoimmune therapy is the immune checkpoint protein V-type immunoglobin domain-containing suppressor of T cell activation (VISTA) or programmed dealth-1 homolog (PD-1H) of the B7 family. VISTA acts as both a ligand [on antigen presenting cells (APCs) and other cells] and as a receptor (on T cells). It functions as an immuno-suppressor by decreasing T cell proliferation, balancing the T cell/T regulatory cells (Tregs) ratio, and inhibiting cytokine production and inflammation. For the treatment of autoimmunity, an agonist anti-VISTA mAb is needed to interact and activate the inhibitory intracellular signaling pathways that result in the inactivation of the autoimmune T cells. New developments such as VISTA.cartilage oligomeric matrix protein (VISTA.COMP) and anti-human VISTA (anti-hVISTA) mAbs 7E12 and 7GF are potential drug candidates to help downregulate autoimmune responses and reduce the inflammatory states of patients with autoimmunity.