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Immunologic 'Bait and Switch' May Be Key to Treating Autoimmune Disease And Improving Outcome of Organ and Tissue Transplantation

St. Jude Researchers Successfully Treat Autoimmune Brain Disease in Mice By Luring Rogue Immune Cells to Their Deaths With Genetically Engineered Bait

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Nov. 15, 2002
PRNewswire
Tenn.,

Researchers at St. Jude Children's Research Hospital have demonstrated that it may be possible to improve treatment of autoimmune diseases like multiple sclerosis, and prevent rejection of transplanted organs and tissues.  The research involves using cells carrying a genetically engineered protein "bait" to lure specific types of rogue immune system cells to their deaths.

The St. Jude strategy pitted the genetically engineered (transgenic) immune cells called T lymphocytes against a population of T cells that cause a brain disease, experimental allergic encephalomyelitis (EAE). This autoimmune disease is artificially provoked in mice and used by researchers as a model to study brain diseases that destroy the protective covering of nerves. Transgenic T cells injected into the mice significantly reduced brain damage by destroying the rogue immune cells that caused EAE. Autoimmune diseases occur when some cells of the immune system attack certain tissues or organs in the body instead of protecting against foreign invaders.

The preliminary finding offers hope for treating a variety of serious and often deadly autoimmune diseases caused by T cells in humans, including multiple sclerosis and rheumatoid arthritis. The technique also may be useful for slowing or preventing the body's rejection of transplanted organs and tissues, according to Terrence Geiger, M.D., Ph.D., the lead author of a report on this work, which appears in the December 2002 issue of Nature Biotechnology.

Because such therapy would target only the immune system cells causing the disease, such treatments will probably only cause mild, if any, side effects in patients, according to Geiger.

"These are exciting findings that suggest a new approach to treating certain immunologic diseases," said Geiger, a member of the Department of Pathology at St. Jude. "Although not ready for clinical use now, it is a proof of principle that will guide our efforts over the next several years to understand how best to bring this technology to the bedside."

Engineering the Bait and Switch

Geiger's group genetically engineered a type of T cell, called CD8+. Then they dangled "bait" to lure the rogue, autoimmune T cells that cause EAE. This bait was in the form of receptors that the rogue cells recognized and attached to, springing the deadly trap. Once the autoimmune T cells grabbed the bait, the CD8+ eliminated or suppressed those autoimmune T cells.

The CD8+ continued to reduce symptoms even 50 days after the start of treatment, showing that the benefits of this therapy in mice are durable.

Key to the St. Jude team's success was its ability to link together a set of genes that made the immunologic bait. One end of this bait was anchored inside the transgenic T cells, while the other end projected outside.

The bait included a copy of the protein that the rogue immune cells were targeting in the brain cells. This tricked those autoimmune cells into thinking they were attacking brain cells. The protein was linked with standard immune system signaling molecules that direct the response of immune system cells to specific signals.

"The technique, if successful in follow-up studies, may be very powerful because it's so versatile," Geiger says. "By choosing various, specific cells to engineer with different kinds of bait, we might be able to design treatments for many different immunologic diseases."

The research was supported by the National Institutes of Health; ALSAC, the fundraising arm of St. Jude; and the Howard Hughes Medical Institute.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is supported through funds raised by ALSAC. ALSAC covers all costs not covered by insurance for medical treatment rendered at St. Jude Children's Research Hospital. Families without insurance are never asked to pay. For more information, please visit
http://www.stjude.org.

SOURCE St. Jude Children's Research Hospital
 

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