Suppression of Cell-Mediated Immunity by Down-regulation of Interleukin-12

Inventor(s)

Giorgio Trinchieri, Maria Wysocka, and Christopher L. Karp

Tech ID
TG96001
Background

The cytokine interleukin-12 (IL-12), which is produced during the immune response to a variety of stimuli, is critical for the development of cell-mediated immunity. Among its various functions in vivo, IL-12 is a potent inducer of interferon-gamma production by T lymphocytes and natural killer (NK) cells and is a co-factor in the mitogenic stimulation of these cell types. However, inappropriate cell-mediated immune responses, often accompanied by over-expression of IL-12, have been identified as having a key role in the development of a variety of autoimmune disorders, such as rheumatoid arthritis, multiple sclerosis, graft-versus-host disease, diabetes mellitus, systemic lupus erythematosus (lupus), and Crohn's disease. Reduction of IL-12 levels, for example by administration of antibodies to IL-12, has been effective in controlling autoimmune diseases in animal models.

 

Researchers at the Wistar Institute have determined that blockage of some complement receptors, including CD46 (the cellular receptor for measles virus) and CR3, can down-regulate production of IL-12 by monocytes. These findings support the well-known suppression of cell-mediated immunity following measles infection. Therefore, compounds that bind to these complement receptors, such as antibodies or other proteins, may be effective in reducing the production of IL-12 in autoimmune diseases and other conditions in which this cytokine is over-produced.

Key Words
anti-inflammatory, autoimmune disease, immune diseases, immunotherapy, Therapeutic
Applications and Advantages

Antibodies and other ligands that bind to CD46 and other complement receptors may be developed for treatment of a variety of auto-immune disorders, including arthritis, graft-versus-host disease, lupus, multiple sclerosis and Crohn's disease.

Intellectual Property Status

U.S. Patent No. 6,086,876.

Licensing Opportunity

Wistar is seeking an exclusive license for this technology.