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Basel, 23 August 2004

New perspectives in the fight against autoimmunity
Roche researchers discover that a naturally occurring peptide influences immune response

The September issue of Nature Immunology reports that researchers at Roche Basel in collaboration with immunologists at the Harvard Medical School, Boston, MA have discovered a naturally occurring peptide that could play a pivotal role in the fight against autoimmune diseases. The so called CLIP (class II associated invariant chain peptide) lowers the production of those cells of the immune system that are critical in triggering pro-inflammatory immune responses, including autoimmunity. This finding may give rise to new therapeutic strategies in particular in the field of rheumatoid arthritis (RA).

“RA belongs to the group of autoimmune diseases that depend on the expansion of a subset of blood cells – so called helper T lymphocytes (TH1)”, explained Harald Kropshofer, Ph.D., Roche Head Non-clinical Immunology. “Particular TH1 cells contribute to autoimmunity by recognizing proteins of our own body, thereby triggering adverse reactions of the immune system against the body’s own tissues. At a certain stage, these TH1 cells begin to secrete hormone-like substances, such as interferon-gamma (IFN-γ), interleukin-2 (IL-2) or interleukin-6 (IL-6), that can trigger, mediate and maintain autoimmune diseases. Hence, a peptide that helps to lower the generation rate or abundance of these TH1 cells could be an extremely helpful approach in RA therapy”.

Kropshofer’s team, along with one led by Anne Vogt, Ph.D., Head Applied Immunology, Roche Center for Medical Genomics, could show in a series of preclinical studies that specialized cells of the immune system, termed ‘dendritic cells’, turn on the natural occurring peptide CLIP on the cell surface which reduces the number of helper T cells changing to the TH1 type. Thus, CLIP appeared to function as a novel type of peptide regulator. More important, the researchers found that synthetic CLIP had the same function as naturally occurring CLIP. This opens up the possibility of using synthetic CLIP or variants thereof as therapeutic agents. CLIP mediates its activity by binding to molecules of the major histocompatibility complex (MHC) class II which are being viewed as risk factors for RA and other autoimmune diseases.

“The potential pharmacological importance of this discovery comes from the fact that modulating levels of CLIP may be used to modulate the immune response itself,” said Ira Mellman, Department Head Ludwig Institute of Cancer Research, Yale University, New Haven.

About Autoimmune Diseases
Autoimmune diseases are a number of disorders, most of them serious, resulting from an inappropriate or excessive response by components of the immune system. The cause is a breakdown in the mechanisms controlling immunological tolerance to the body’s own tissues. As a result, antibodies or certain T lymphocytes attack the body’s own proteins or healthy cells. For Roche’s immunologists, findings from basic research are the cornerstone of the quest for novel, highly specific medicines aimed as closely as possible at the root causes of autoimmune diseases and rejection reactions following organ transplantation.
A long list of clinical entities are recognised as autoimmune diseases, including multiple sclerosis, certain types of diabetes, and rheumatoid arthritis.
Based on the need for more effective treatments, Roche is currently investigating seven compounds in early stage clinical development for autoimmune diseases as well as RA.

Rheumatoid Arthritis (RA)
Rheumatoid arthritis (RA) is a progressive, systemic autoimmune disease characterized by inflammation of the membrane lining in joints. This inflammation causes a loss of joint shape and alignment, resulting in pain, stiffness and swelling, ultimately leading to irreversible joint destruction and disability. Characteristics of RA include redness, swelling, pain, and movement limitation around joints of the hands, feet, elbows, knees and neck. In more severe cases of RA the eyes, lungs or blood vessels may be involved. RA may also shorten life expectancy by affecting major organ systems.
RA is one of the most common forms of autoimmune disease and affects more than 6 million people worldwide.

About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is number one in the global diagnostics market and is the leading supplier of pharmaceuticals for cancer and a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche employs roughly 65,000 people in 150 countries. The Group has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai.

Further information:
- Nature: www.nature.com 
- Harvard Medical School: hms.harvard.edu/hms/home.asp  
- Yale Cancer Center: www.med.yale.edu/ycc/index2.htm 

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