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

Patent metadata

Field	Value
Publication number	US-9631018-B2
Application number	US-201113637381-A
Country	US
Kind code	B2
Filing date	Mar 25, 2011
Priority date	Mar 26, 2010
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

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 arthritic conditions such as RA.

First claim

What is claimed is:

1. A method of treating ovarian cancer in a patient in need thereof by administering an effective amount of an anti-human V-region Immunoglobulin-containing Suppressor of T Cell Activation (“VISTA”) protein antibody or antigen-binding antibody fragment, wherein such antibody or antigen-binding antibody fragment, inhibits the immunosuppressive effects of VISTA protein.

2. The method of claim 1 , wherein said cancer is in early (non-metastatic) form.

3. The method of claim 1 , wherein said cancer is metastatic.

4. The method of claim 1 , wherein the anti-human VISTA antibody is an intact antibody.

5. The method of claim 1 , wherein the anti-human VISTA antibody or antigen-binding fragment is polyclonal or monoclonal.

6. The method of claim 1 , wherein the anti-human VISTA antibody or antigen-binding fragment is a human or humanized antibody or antigen-binding fragment thereof.

7. The method of claim 1 , wherein the anti-human VISTA antibody or antigen-binding fragment is a chimeric antibody.

8. The method of claim 1 wherein the patient prior to treatment is found to express elevated levels of VISTA protein on immune cells.

9. The method of claim 1 , wherein the patient is further receiving radiotherapy, chemotherapy or another anti-cancer biologic.

10. The method of claim 9 wherein the patient prior to treatment has an ovarian cancer that does not respond to said radiotherapy, chemotherapy or said anti-cancer biologic.

11. The method of claim 1 , wherein the anti-VISTA antibody or antigen-binding antibody fragment specifically binds to an epitope comprised in the IgV or stalk region of human VISTA protein.

12. The method of claim 1 , wherein the anti-VISTA antibody or antigen-binding antibody fragment elicits one of the following activities: (i) upregulates cytokine production by T cells; (ii) induces expansion of T cells, (iii) promotes antigen specific T cell immunity; or (iv) promotes CD4 + and/or CD8 + T cell activation.

Assignees

• Noelle Randolph J
• Wang Lili
• Dartmouth College

Inventors

• Noelle Randolph J
• Wang Lili

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/08

  Vasodilators for multiple indications · CPC title

• A61P39/02

  Antidotes · CPC title

• A61P5/38

  of the suprarenal hormones · CPC title