Immunomodulating tumor necrosis factor receptor 25 (tnfr25) agonists, antagonists, and immunotoxins

Abstract

This document provides novel compositions and methods utilizing immunomodulating agents that can stimulate or indirectly augment the immune system, or can have an immunosuppressive effect. TNFR25 agonists disclosed herein have an anti-inflammatory and healing effect. They can be used, e.g., to treat disease caused by asthma and chronic inflammation, such as inflammatory bowel diseases including ulcerative colitis and Crohn's Disease. TNFR25 antagonists disclosed herein can inhibit CD8 T cell-mediated cellular immune responses and can, for example, mitigate organ or tissue rejection following a tissue transplantation. TNFR25 agonists disclosed herein represent biological response modifiers that alter the interaction between the body's cellular immune defenses and cancer cells to boost, direct, or restore the body's ability to fight the cancer when given with tumor vaccines. TNFR25 specific immunotoxins disclosed herein are also capable of increasing the effectiveness of a chemotherapeutic regimen by depleting a cancer patient of naturally occurring immunosuppressive cells.

What is claimed is: 
     
         1 . A method for modulating antigen-specific T cell expansion in a subject, the method comprising the steps of:
 (a) administering to the subject a cell expressing a foreign antigen; and   (b) administering to the subject an amount of an agent which specifically binds TNFR25 effective to expand T cells specific for the foreign antigen in the subject.   
     
     
         2 . The method of  claim 1 , wherein the agent is an agonistic anti-TNFR25 antibody. 
     
     
         3 . The method of  claim 1 , wherein the agent is a soluble TL1A protein. 
     
     
         4 . The method of  claim 1 , wherein the cell is allogeneic to the subject. 
     
     
         5 . The method of  claim 1 , wherein the cell is a cancer cell.