The National Institute of Allergy and Infectious Diseases (NIAID) is spearheading a $144 million initiative to develop new ways of inducing immune tolerance -- selectively modulating the immune system by inhibiting harmful immune responses while keeping protective ones intact. The strategy promises to improve the success of transplants and treatments for autoimmune diseases that destroy the body's own cells. The research could lead to better management of type 1 diabetes, lupus, arthritis and other immune system disorders.
The project, known as the Collaborative Network for Clinical Research on Immune Tolerance, will involve nearly 40 research institutions internationally. Jeffrey Bluestone, Ph.D., director of the Ben May Institute for Cancer Research at the University of Chicago, was named director of the network.
"This collaboration brings together some of the brightest minds in immunology and flows from NIAID's plan to accelerate clinical trials for novel approaches to modulate immune responses," says NIAID Director Anthony S. Fauci, M.D. "Immune tolerance research has great potential to help millions afflicted with some of the most debilitating and chronic immune-mediated diseases."
The seven-year initiative was announced at a University of Chicago press briefing about grants from NIAID and the Juvenile Diabetes Foundation International. JDF is co-sponsoring the initiative along with the National Institute of Diabetes and Digestive and Kidney Diseases, which also conducts and supports research in immune modulation. NIAID and NIDDK are components of the National Institutes of Health (NIH) within the U.S. Department of Health and Human Services.
Network researchers will conduct clinical trials to improve the success of kidney transplants using "tolerogenic approaches." Such therapies selectively disable the immune cells responsible for attacking transplanted organs while allowing other immune cells to function normally as defenders against invading bacteria, viruses and cancer cells.
Similar clinical trials are planned for patients receiving transplanted human islets to treat juvenile or type 1 diabetes, a disease caused by the autoimmune destruction of insulin-producing cells in the pancreas. Network investigators will test similar therapeutic approaches for other autoimmune diseases, such as systematic lupus erythematosus, rheumatoid arthritis and multiple sclerosis, and will pursue better ways to measure immune tolerance in humans. Eventually, the network will expand into clinical trials in immune modulation to treat asthma and allergic diseases as well.
Researchers have long sought ways to improve the success of organ, tissue and cell transplantation. Currently, standard treatment for the more than 19,000 people receiving transplants each year in the United States involves drugs that suppress the entire immune system. Unfortunately, such medications have many harmful side effects, including lowering resistance to infections and cancer, and they do not guarantee freedom from rejections or long-term survival of transplants. More than half of transplanted kidneys fail to survive 10 years.
Attempts at islet transplantation, an experimental therapy that replaces pancreatic islets destroyed by type 1 diabetes, have been even less successful. Only about 5 percent of people with diabetes who receive transplanted islets along with immunosuppressive drugs are able to stay off insulin longer than one year.
Recent tests of tolerogenic approaches to induce immune tolerance have shown promising results in both laboratory animal models and early human clinical studies. Network researchers will accelerate testing of these and other tolerogenic approaches, and will develop and evaluate methods to monitor the induction, maintenance and loss of immune tolerance in humans.
"We have established a collaboration that will be open and inclusive, with the flexibility to capitalize on emerging opportunities for any potential tolerogenic approaches," says Dr. Bluestone. A recognized pioneer in developing tolerogenic therapy, Dr. Bluestone was also named director of a separate new JDF Center for Islet Transplantation at the University of Chicago and the University of Minnesota.
The NIAID award will supply nearly $130 million for the network, with another $14 million provided by the JDF, the world's leading nonprofit, nongovernmental funder of diabetes research. NIDDK is also contributing to the project.
"This represents one of the largest NIH awards for clinical research and the first program for cross-disciplinary research on immune tolerance," says Daniel Rotrosen, M.D., director of NIAID's Division of Allergy, Immunology and Transplantation. "The network addresses growing congressional and public interest in transplantation, and in autoimmune and allergic diseases. Establishment of the network represents a major step in meeting the recommendations of the congressionally mandated Diabetes Research Working Group and other NIH advisory panels, and is indicative of NIAID's commitment to improving health for patients with a broad range of immune-mediated diseases."
Participating with the University of Chicago to form the network are the following:
- Australian National University, Canberra, Australia
- Beth Israel Deaconess Medical Center, Boston, MA
- Brigham and Women's Hospital, Boston, MA
- Cleveland Clinic Foundation, OH
- Columbia University,New York, NY
- Corixa Corporation, Seattle, WA
- Cornell University, Ithaca, NY
- Duke University, Durham, NC
- Emory University, Atlanta, GA
- Genetics Institute, Cambridge, MA
- Harvard University, Boston, MA
- Johns Hopkins University, Baltimore, MD
- Justus-Liebig University, Giessen, Germany
- Kaiser Hospital, San Diego, CA
- Massachusetts General Hospital, Boston
- Mt. Sinai School of Medicine, New York, NY
- National Jewish Medical Center, Denver, CO
- Naval Medical Research Center, Bethesda, MD
- Ohio State University, Columbus
- Scripps Research Institute, La Jolla, CA
- Stanford University, CA
- University of Alabama at Birmingham
- University of Alberta, Canada, Edmonton
- University of California, San Diego
- University of California, San Francisco
- University of Cincinnati, OH
- University of Colorado, Boulder
- University of Florida, Gainesville
- University of Italy, Milan
- University of Massachusetts, Boston
- University of Miami, FL
- University of Michigan, Ann Arbor
- University of Minnesota, Minneapolis-St. Paul
- University of Pennsylvania, Philadelphia
- University of Washington, Seattle
- University of Wisconsin, Madison
- Washington University, St. Louis, MO
- Yale University, New Haven, CT
- Yeshiva University, New York, NY