Baylor Institute for Immunology Research (BIIR) is celebrating its 10th anniversary this year, capping a decade of advances in understanding the immune system and developing new treatments for cancer (melanoma, breast and prostate cancers), autoimmune diseases (lupus, rheumatoid and juvenile arthritis, and Type 1 diabetes), and infectious diseases (influenza and HIV), as well as reducing organ transplant rejection.
Established in 1996 as the immunology research component of Baylor Research Institute, BIIR brings together laboratory scientists and clinicians in an effort to increase understanding of how the human immune system works. Led by director Jacques Banchereau, Ph.D., an internationally renowned immunologist, the Institute is devoted to rapidly translating basic laboratory discoveries made about the immune system into effective treatments for humans.
The interdisciplinary program focuses on developing new therapies, such as using patients’ own blood-derived dendritic cells to modulate immune responses in beneficial ways. BIIR is using this technique to research potential vaccines for melanoma, prostate cancer, breast cancer, lymphoma and HIV.
"No other institute that I know of is dedicated solely to human immunology basic research and the direct translation of discoveries into clinical trials," says Dr. Banchereau. "Over the last 10 years we have made significant advances in the field of human immunology that have already resulted in the improved health of many patients, most particularly children with a severe form of arthritis."
"The common link between cancer, infectious diseases, autoimmunity and allergy is an alteration of the immune system. So the idea behind developing this institution was to create a place where all the experts in these disciplines could talk to each other," explains Dr. Banchereau. "Our interdisciplinary program is unlike traditional scientific institutions, but our unique approach is very important because a discovery in one area may be helpful to another."
A critical element of success in this challenging area of improving human health is the ability to develop large-scale collaborative efforts. Since the establishment of BIIR, Baylor Research Institute has collaborated with more than 40 research organizations worldwide and has been awarded more than $40 million in outside or competitive grants for research funding.
One of the unique aspects of BIIR is a concentration of research on human dendritic cells. Dendritic cells are a class of white blood cells that initiate and control the body’s overall immune response. They reel in invaders, such as bacteria or viruses, chop them into pieces called antigens, and display the antigens on their surfaces. Antigen-bearing dendritic cells travel to lymph nodes or the spleen, where they tell cells of the immune system—B cells, which make antibodies, and killer T cells, which attack infected cells—how to respond against the invader. Some cells educated by dendritic cells become "memory" cells that remain in the body for years—perhaps decades—to combat the invader in case it returns. Dendritic cells are essential in the process of vaccination and studying them naturally leads to the development of new vaccines, a focus of BIIR.
To view computer animation of how a dendritic cell vaccine for melanoma works, visit www.BIIR.org.
Areas of Research Using Dendritic Cell Technology
Dr. Banchereau, together with Joseph Fay, M.D. and Karolina Palucka, M.D., Ph.D., has established dendritic cell vaccines for metastatic melanoma. Since 1998, more than 500 personalized vaccines have been manufactured and used to treat more than 90 patients diagnosed with late-stage metastatic melanoma in Phase I and Phase II clinical trials. Immune responses were observed in several patients. These patients had all failed other therapies and would not have been expected to survive. In some patients dendritic cell vaccination led to durable objective tumor regressions, as for example in one of the trials with overall 10 percent objective response rate. Altogether, retrospective analysis of overall survival in a group of 66 patients, accrued between 1999 and 2003, showed 20 percent long-term survival. These promising results now need to be confirmed in larger prospective randomized trials.
To view the testimonial of a patient who was diagnosed with stage IV melanoma and seven years later after receiving the vaccine is still in remission, visit www.BIIR.org.
Researchers at BIIR are currently investigating the development of a personalized vaccine for breast cancer patients using dendritic cells. "The goal of the therapy is to stimulate the immune system to destroy breast cancer tumor cells throughout the body," says A. Karolina Palucka, M.D., PhD, BIIR cancer immunologist and lead investigator of the study.
A paper published earlier this year in the Journal of Experimental Medicine, reported that breast cancer cells hijack a particular immune system pathway, leading to the development of tumors. The research, led by Dr. Palucka and Dr. Banchereau, identified a key mechanism in the growth and development of breast cancer tumors, opening up new treatment strategies.
In 2006, Wenru Song, M.D., Ph.D., a medical oncologist, was recruited from Stanford University in a joint appointment between Baylor Research Institute and Texas Oncology, P.A. Dr. Song and his colleagues at Stanford developed a new type of combined cancer therapy that he is testing in a Phase I clinical trial at BIIR. A vaccine composed of a patient’s own dendritic cells is injected directly into the patient’s tumor. This vaccine strategy is used in combination with chemotherapy or local cancer therapy.
Other Customized Cancer Vaccines
In 2004, Baylor Health Care System formed its first biotech company, ODC Therapy Inc., to develop, produce and distribute customized cancer vaccines, including an individualized melanoma vaccine. Plans are under way to develop other personalized therapies for various types of cancer.
Systemic lupus erythematosus (lupus) is a very aggressive autoimmune disease. This disease can damage kidneys, skin, heart and other organs in children and can be fatal without early treatment. Researchers at BIIR, under the leadership of Virginia Pascual, M.D., have linked abnormal secretion of alpha interferon (a naturally produced anti-viral protein) to the malfunctioning immune systems of young patients with lupus. This finding is a major step toward explaining how lupus deceives the body’s immune system into destroying healthy cells and suggests new therapeutic approaches. In fact, BIIR researchers have developed an antibody against alpha interferon that has been licensed to Argos Therapeutics and Novo Nordisk. These companies will collaborate with Baylor Research Institute to manufacture this antibody and perform clinical trials.
In 2006, Baylor Research Institute was awarded a $6.2 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, one of the National Institutes of Health, to establish a Center for Lupus Research. This project is led by Dr. Pascual, an investigator at BIIR and a practicing pediatric rheumatologist.
Dr. Pascual and her collaborators also have reported the successful treatment of children with systemic onset juvenile idiopathic arthritis (SoJIA). This was a disease of unknown origin until recently, when Dr. Pascual’s group demonstrated that these patients’ blood cells were producing excess levels of interleukin-1b (IL-1b), a key factor in inflammation. To test the hypothesis that over-production of IL-1b might play a significant role in SoJIA and that inhibiting IL-1b activity could be beneficial, nine SoJIA patients received a drug that inactivated IL-1. All nine patients responded to some degree to the therapy.In the eight patients who had active arthritis, the researchers observed decreases in arthritic symptoms in the joints, as well as improvement of hemoglobin levels, white blood cell count and a number of other indicators of arthritis. They found that the therapy completely restored the function of six of the eight patients and lessened the symptoms of the remaining two. These studies were published in the Journal of Experimental Medicine in 2005 and 2007.
To view the testimonial of a parent whose child was diagnosed with SoJIA and today is healthy, visit www.BIIR.org.
Scientists at BIIR also are studying ways to induce tolerance of transplanted organs. The goal is to turn off a patient’s immune system response against a foreign organ and to accept the organ immediately, avoiding rejection and the need for patients to take immunosuppressive drugs. To recognize which patients have developed immunotolerance, Baylor scientists, led by Damien Chaussabel, Ph.D., are using microarray technology that was developed through their research on cancer and autoimmunity. Using a small amount of blood from a patient, the microarray machine scans 43,000 different genes and shows their activity. This activity is shown as bars of changing color. Baylor scientists have identified unique color patterns or "signatures" that correspond to specific disease processes, infections and allergic responses.
"This is where our research is headed," says Michael A.E. Ramsay, M.D., president of Baylor Research Institute. "In the future, we’ll be able to diagnose illnesses with just a few drops of blood by analyzing which genes have been activated and which have been suppressed. For example, if someone gets off an airplane with a fever, we’ll be able to take a small blood sample, and, in just a few hours, determine if it’s avian influenza or another viral or bacterial infection."
Dr. Ramsay says that this same technology will benefit transplant patients and patients with autoimmune diseases like lupus, diabetes, multiple sclerosis, rheumatoid arthritis, psoriasis and inflammatory bowel disease. By screening patients through blood analysis, physicians will be able to treat organ rejection or a flare-up of disease before there are any clinical symptoms and before any organ damage has occurred.
This year, BIIR, Baylor Research and the Baylor Regional Transplant Institute recruited Shinichi Matsumoto, M.D., Ph.D., to head up its islet cell transplantation program. Dr. Matsumoto is a world-renowned expert in islet cell transplantation. In type 1 diabetes, a person’s immune system attacks the pancreatic islet cells that produce insulin. Dr. Matsumoto has pioneered many advances in the isolation of islet cells for transplantation. He is the only researcher in the world to perform an islet cell transplant from a living donor.
In 2003, Baylor Research Institute received a $14.6 million grant from the National Institute of Allergy and Infectious Disease (NIAID) to create the Baylor/NIAID Center for Translational Research on Human Immunology and Biodefense. With this funding, investigators are studying the human immune system’s response to emerging pathogens and other virulent agents. They are seeking to develop more effective vaccines against these threats. Gerard Zurawski, Ph.D., joined BIIR in 2004 to lead this effort. Previously, Dr. Zurawski was the Senior Director in Molecular Biology at Schering-Plough Biopharma. "Thanks to the hard work of our talented multi-disciplinary team", says Dr. Zurawski, "we are rapidly moving our novel vaccines into animal and human testing."
Human Immunodeficiency Virus (HIV)
The World Health Organization (WHO) estimates that in 2006 nearly 40 million people worldwide were living with AIDS. According to WHO, there were 2.3 million new cases and 2.9 million deaths due to AIDS last year alone. BIIR researchers are actively pursuing the development of HIV vaccines based on their work in dendritic cell biology. Building on their successes in cancer vaccines, BIIR will produce two types of HIV vaccines, one that should prevent infection in healthy people and the other that will treat HIV-infected people. Within the next several months, a new vaccine to treat HIV patients will begin being tested in a Phase I clinical trial.
Additional milestones reached since the opening of BIIR include the establishment of three endowed chairs at Baylor Research Institute. In 2004, Dr. Banchereau was appointed to the W. W. Caruth, Jr. Chair in Organ Transplantation Immunology at Baylor Research Institute. The goal of this research is to prevent rejection of organs in transplant patients and establish tolerance by manipulating the immune system. Anna Karolina Palucka, M.D., Ph.D., was appointed in 2004 to the Michael A.E. Ramsay Chair for Cancer Immunology Research. Dr. Palucka’s research concentrates on the use of dendritic cell vaccines to develop new therapies for patients with cancer. The search is ongoing to fill the vacant Max and Gayle Clampitt Chair in Infectious Disease Research.
BIIR has grown rapidly in the last several years. "We began with five members and by the end of this year, we will have nearly 100. We are bursting at the seams", says Dr. Banchereau. "We have been very fortunate with the extraordinary support of Baylor Health Care System and local philanthropists, who are critical to our continued successes."
Within the next year, BIIR will recruit two Deputy Directors to help coordinate the numerous research initiatives and will expand to additional facilities on the Baylor University Medical Center at Dallas campus as well as to Baylor All Saints Medical Center at Fort Worth.
"We are very excited about the prospects for the next 10 years, and beyond", states Dr. Banchereau.
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