National Institute of Diabetes and Digestive Diseases
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
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
"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
Participating with the University of Chicago to form the network are the