Vista regulatory t cell mediator protein, vista binding agents and use thereof

Abstract

The present invention relates to a novel regulatory T cell protein. This protein, designated PD-L3 OR VISTA resembles members of the PD-L1 family, identified a novel and structurally-distinct, Ig-superfamily inhibitory ligand, whose extracellular domain bears homology to the B7 family ligand PD-L1. This molecule is designated as PD-L3 OR VISTA or V-domain Immunoglobulin Suppressor of T cell Activation (VISTA). Expression of VISTA is primarily within the hematopoietic compartment and is highly regulated on myeloid APCs and T cells. Therapeutic intervention of the VISTA inhibitory pathway represents a novel approach to modulate T cell-mediated immunity for the treatment of a wide variety of cancers, e.g., ovarian, bladder cancer and melanomas. Also, VISTA proteins, especially multimeric VISTA proteins and antibodies may be used to suppress T cell immunity in autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis and artritic conditions such as RA.

1 . An isolated, or recombinant immunosuppressive multimeric VISTA protein or conjugate thereof that comprises at least of two copies of a polypeptide which is at least 90% identical to the extracellular domain of the human or murine VISTA polypeptide in SEQ ID NO:2 or 4 which contains at least two copies of a polypeptide which is at least 90% identical to a fragment of the extracellular domain of said VISTA polypeptide which is at least 50 amino acids along. 
     
     
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