CCIS Center For Clinical Immunology At Stanford

CCIS Philosophy

The Nature of the Problem

Allergic and immune system diseases affect nearly 20 percent of Americans. These conditions, which include asthma, type 1 diabetes, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, psoriasis and acquired immune deficiency syndrome (AIDS), lead to chronic debilitation, life-long illness, and premature mortality while resulting in insurmountable medical costs. Excessive or depressed immune function plays a key role in these autoimmune diseases, in the rejection of transplanted organs and tissues, and in the body's inability to fight invading cancer cells.

Although these types of diseases affect a large percentage of the population, few specific therapies and mechanisms target their prevention and cure. Individuals and families have long faced frustration in their quest for relief. Breakthroughs in science have advanced basic understanding of the immune system, but such breakthroughs have often lain fallow because the traditional structures of medicine have not promoted the easy transfer of ideas generated in the laboratory to the bedside of the patient.

Scientists and clinicians at Stanford have concluded that these diverse diseases should be investigated and managed under a cohesive paradigm-- classified together according to their common characteristics rather than managed and treated separately by clinical specialists. Rather than conducting disease-specific research, scientists undertake studies at the genetic and molecular levels in order to understand the shared pathophysiology of the disease and provide answers for a variety of common problems.

The Center for Clinical Immunology at Stanford has been established to reflect this new paradigm. The Center has brought together physician scientists from throughout the medical center to facilitate daily collaboration. Enhanced opportunities have enabled clinicians and investigators to translate cutting-edge basic science into treatments covering the entire spectrum of diseases of the immune system.

The Role of Stanford Scientists

Today's faculty build on the research of Stanford scientists who laid the foundation for clinical advances in the treatment of some of the most devastating human diseases. Two of Stanford's Nobel laureates -- Dr. Arthur Kornberg and Dr. Paul Berg -- and the internationally renowned Dr. Stanley Cohen are among the architects of the genetic revolution. Their work, which helped to spawn a new generation of research in molecular medicine, has completely transformed the nature of medical research and has enabled scientists to make great strides in the diagnosis and treatment of immune disorders.

Stanford microbiologist and immunologist Dr. Hugh McDevitt works on the next frontier of medicine -- preventing disease before it strikes. He has found a direct genetic relationship between a person's immune response genes and the resistance to such diseases as type I diabetes. Currently he is working on a means to control a patient's autoimmune response to the antigens that are related to type I diabetes. His colleague, Dr. C. Garrison Fathman, who directs the Center for Clinical Immunology, conducts research on developing new therapies for autoimmune diseases. Dr. Fathman directs a National Institutes of Health-funded Prevention of Autoimmunity program where scientists are trying to understand the genetic and immunologic events that trigger the immune system to start recognizing self tissues as foreign and begin attacking them.

A host of other research milestones have occurred at Stanford that are critical to modern immunology research:

• 1984: the isolation of a gene coding for part of the T-cell receptor, a key to the immune system's function.
• 1987: the use of T-cell specific (anti-CD4) antibodies to allow allograft transplantation tolerance.
• 1988: the isolation of pure hematopoietic stem cells from mice.
• 1988: the use of T-cell specific (anti-CD4) antibodies to treat autoimmune disease.
• 1989: the discovery of the "homing receptor," which guides the white blood cells of the immune system into sites of inflammation.
• 1992: the use of peptides of antigens to treat animal models of multiple sclerosis.
• 1992: the development of treatment to enhance patients' immunological response against B-cell lymphoma with a genetically engineered vaccine from their own tumors.
• 1993: the discovery of a protein that appears to be involved in the development of type 1 diabetes and allowed the prevention of the disease in mice.
• 1996: the use of "dendritic cells" loaded with purified tumor-specific antigens to create an immune response to treat refractory cancer.

From Research to Therapy

The CCIS cross-disciplinary approach has hastened Stanford scientists' abilities to translate research discoveries into clinical treatments. The CCIS also trains a new generation of physician scientists to explore the common elements of immune-based disorders and to extend the concepts of basic immunology to their diagnosis and management. Located within a world-renowned research university such as Stanford, the center is strategically placed to transfer new knowledge from the laboratory to the patient and back to the laboratory.

One example of this transfer has been the recent development of the Diabetes Prevention Trial 1. This is a multi-center attempt to use the knowledge gained in preclinical experiments in animal models of insulin-dependent diabetes mellitus (IDDM) to diagnose and treat IDDM before it becomes clinically apparent in humans.

In another clinical trial, researchers harvest immune system cells from related donors (follicular-dendritic-antigen-presenting cells) and load them with portions of the HIV virus to induce specific immune responses in an attempt to block the progressive infection and immune system deterioration that comprise AIDS. The researchers also use "antigen-presenting cells" to immunize patients to their own cancers by loading them with protein fragments of tumor specific antigens.

Given the nature of scientists' understanding of the complexity of diseases of the immune system, many more such clinical trials should be undertaken. The Center for Clinical Immunology at Stanford will maximize the potential to expand collaborative research and to bring the results quickly to clinical trial, offering patients access, without delay, to innovative therapies.

An Intellectual Home

The Center for Clinical Immunology at Stanford has made its home in the recently constructed Center for Clinical Sciences Research. Expanding the boundaries of science, this state-of-the-art facility houses the Center for Cancer Research and the Center for Applied Human Genetics in addition to the CCIS. Designed by the internationally distinguished architect, Sir Norman Foster, the new building is a four-story, 185,000 square-foot structure with specialized laboratories and core facilities. The building's design has:


• encouraged day-to-day communication among scientists as they urge one another on in the search for new strategies to diagnose, prevent and cure human disease.
• provided open laboratories, broad stairways, strategically located meeting spaces, and a center courtyard to offer ample opportunities for personal interaction.
• taken advantage of the most advanced telecommunications technology to promote and nurture collaborations among the physician scientists housed in the building, and to reinforce communications between center scientists and their colleagues elsewhere at Stanford (via the Stanford Instructional Television Network), throughout the community, and around the world (via the Internet).

The new building has provided opportunities for researchers within the CCIS to interact with their colleagues in adult and pediatric cancer research; gene therapy, clinical imunology and other related areas of study.

From Vision to Reality

The Center for Clinical Immunology at Stanford seeks private support to fund new program development, recruitment of outstanding scientists, and construction of state-of-the-art research laboratories within the new facility. By teaming with the philanthropic community, the Center for Clinical Immunology at Stanford can build bridges between discoveries in basic science and their application to human disease. The Center offers a milieu in which medical science can apply its finest tools and talents to diagnose, treat, and cure disorders of the immune system.

Stanford University Medical Center turns to its most generous friends to bring this long-held dream to fruition. Physician scientists at Stanford have changed the odds and restored precious quality of life for thousands. If their accomplishments are grand, the challenge of diseases yet unconquered is greater still. The Center for Clinical Immunology at Stanford is dedicated to that challenge.

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