IMMUNOMODULATING TUMOR NECROSIS FACTOR RECEPTOR 25 (TNFR25) AGONISTS, ANTAGONISTS, AND IMMUNOTOXINS

摘要

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.

主权项

1. A method for enhancing expansion of antigen-specific CD8 T cells in a subject, the method comprising the steps of:
(a) administering to the subject an antigenic composition comprising a cell expressing a gp96-Ig protein engineered to be secreted from the cell, and a cognate antigen of the antigen-specific CD8 T cells, wherein the cognate antigen is a non-self antigen, and wherein administration of the antigenic composition is effective for inducing expansion of the antigen-specific CD8 T cells in the subject; and (b) administering to the subject a TNFR25 agonist in an amount effective to enhance the expansion of the antigen-specific CD8 T cells induced in step (a).