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St. Jude Finds Molecule That Could Improve Cancer Vaccine and Therapy for Other Diseases
Date:11/21/2007

The discovery of a new cytokine called IL-35 could allow clinicians to treat diseases by turning up or down the immune response

MEMPHIS, Tenn., Nov. 21 /PRNewswire-USNewswire/ -- Investigators at St. Jude Children's Research Hospital have discovered a new signaling molecule that prevents immune responses from running amok and damaging the body. The finding could lead to the development of new treatments for cancer, using vaccines; for autoimmune diseases, such as Type 1 diabetes; and for inflammatory diseases, such as inflammatory bowel disease and asthma.

The St. Jude team discovered that specialized immune lymphocytes called regulatory T cells release a protein complex composed of two proteins called Ebi3 and Il12a. This complex acts like a brake on the activity of the aggressive immune cells called effector T lymphocytes. The discovery is important because the manipulation of regulatory T cells is a key goal of immunotherapy. A report on this discovery appears in the journal "Nature" Nov. 22, 2007.

The newly recognized protein complex is one of a large group of signaling molecules called cytokines that cells use to communicate with each other. Since the immune system cytokines are called interleukins, the St. Jude team named this protein interleukin-35 (IL-35). Most cytokines stimulate immune system cells; however, IL-35 is one of the few signaling molecules known to inhibit immune system activity.

"The maximal suppressive function of regulatory T cells depends on IL-35, so blocking IL-35 activity might reduce the ability of T cells to block anti-tumor immune responses," said Dario Vignali, Ph.D., associate member in the St. Jude Department of Immunology, and the paper's senior author. "Treatments that block IL-35 activity may make anti-cancer vaccines more effective and provide new therapeutic opportunities for autoimmune and inflammatory diseases."

"Our findings suggest that controlling levels of IL-35 in patients might one day allow clinicians to dial the immune response up or down depending on the needs of the patient," said Lauren Collison, Ph.D., a postdoctoral fellow in Vignali's laboratory who contributed significantly to the project. Collison is the paper's first author.

Other authors of the paper include Creg Workman, Kelli Boyd, Yao Wang, Kate Vignali and Richard Cross (St. Jude); Timothy Kuo and Richard Blumberg (Harvard Medical School; Boston); and David Sehy (eBioscience, San Diego).

This work was supported by the National Institutes of Health (to D.V. and R.B.), a Cancer Center Support Grant and ALSAC (to D.V.), a St. Jude Gephardt Postdoctoral Fellowship and an NIH Individual National Research Service Award (to L.C.), and the American Liver Foundation (to T.K.).

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit http://www.stjude.org.


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SOURCE St. Jude Children's Research Hospital
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