Virginia Mason served as a clinical trial site for a new oral medication awaiting federal approval that some officials say could be a game-changer for children and adolescents who suffer peanut allergy.

Results of the clinical trials have been published by The New England Journal of Medicine.

The clinical research program at Virginia Mason, in which Virginia Mason Medical Center physicians and Benaroya Research Institute (BRI) scientists collaborate, was one of 66 study sites in 10 countries in North America and Europe. It is believed to have been the largest study of peanut allergy oral immunotherapy to date, with a total of 496 participants who were between four and 17 years old.

An allergy to peanuts is one of the most common food allergies in the United States, according to the American College of Asthma, Allergy& Immunology.  Although more than 1.6 million children and teenagers have peanut allergy, there is currently no approved treatment. The standard of care is a strict peanut-free diet and timely administration of rescue medications when allergic reactions occur. The new medication for which Virginia Mason was a clinical trial site has the potential to change this, supporters said.

Aimmune Therapeutics, the drug manufacturer and clinical trials sponsor, contends the medication would significantly reduce the frequency and severity of allergic reactions to peanuts and lower the risk for potentially life-threatening allergic reactions from accidental exposure. The company announced that, before the end of 2018, it will request approval of the prescription drug by the U.S. Food and Drug Administration.

Benaroya Research Institute at Virginia Mason is an international leader in researching causes of and potential cures for diseases of the immune system, such as allergy and autoimmune disease.

About Virginia Mason Health System

Virginia Mason, founded in 1920, is a nonprofit regional health care system based in Seattle that serves the Pacific Northwest. In the Puget Sound region, the system includes 336-bed Virginia Mason Hospital; a primary and specialty care group practice of more than 500 physicians; outpatient medical facilities and services in Seattle, Bainbridge Island, Bellevue, Edmonds, Federal Way, Kirkland, Issaquah and Lynnwood; Bailey-Boushay House, the first skilled-nursing and outpatient chronic care management program in the United States designed specifically to meet the needs of people with HIV/AIDS; Benaroya Research Institute, which is internationally recognized for autoimmune disease research; Virginia Mason Foundation; and Virginia Mason Institute, which trains health care professionals and others around the world in the Virginia Mason Production System, an innovative management method for improving quality and safety.

Virginia Mason Health System also includes Virginia Mason Memorial, a 226-bed hospital serving Yakima Valley in central Washington since 1950. Virginia Mason Memorial includes primary care practices and specialty care services, including high-quality cardiac care; cancer care through North Star Lodge; breast health at `Ohana Mammography Center; acute hospice and respite care at Cottage in the Meadow; pain management at Water’s Edge; an advanced NICU unit that offers specialty care for at-risk infants; advanced services for children with special health care needs at Children’s Village; and The Memorial Foundation.

Scientists at Benaroya Research Institute at Virginia Mason (BRI) have received a $5 million grant from the National Institutes of Health to accelerate discovery of treatments for peanut allergy through a collaboration involving three BRI labs, Virginia Mason physicians and sponsors of two clinical trials that are continents apart. Food allergy is a large and growing problem, affecting 15 million Americans, with millions of children suffering from life-threatening peanut allergy. While advances have been made, treatment options for people living with peanut allergy remain limited in their effectiveness and longevity.

"Ultimately, this has the potential to truly upend the way we look at food allergy diagnosis and treatment," Jane Buckner, MD, President of Benaroya Research Institute, said of the study.

This two-pronged study will first research peanut allergy patients’ immune responses and classify them into subgroups.  Secondly, researchers will evaluate treatment options being used in a pair of clinical trials to determine how specific treatments can be matched to specific patients to teach their immune systems to tolerate peanut protein.

"We are just beginning to fully understand on a cellular level why some people get peanut allergy and others don’t," said Erik Wambre, PhD, the BRI co-Principal Investigator (PI) of the study. "As we better understand how food allergy works, we can match clinical therapies to individuals’ immune systems."

Researchers will utilize a unique approach in solving this puzzle. "Food allergy is a multifaceted disease with many subtypes. Instead of looking for new allergy immunotherapy therapies, we want to know which therapy should be applied to which patient – that is precision medicine," Dr. Wambre said. "Our goal is high efficacy, high safety. To reach this goal we want to identify an immune signature that can guide treatment decisions and ensure better patient care." In the first part of the study, co-investigators Mary Farrington, MD, David Jeong, MD and David Robinson, MD provide blood samples from their patients at the Virginia Mason Allergy, Asthma and Immunology Clinic. The study’s BRI co-Principal Investigators, Erik Wambre, PhD and William Kwok, PhD will investigate the immune cells from these patients to classify peanut allergy patients into subgroups based on the part of the peanut protein that their immune system reacts to.

For the second part of the study, samples from two ongoing peanut allergy clinical trials will be investigated to pave the way for personalized medicine in food allergy, including the trial, sponsored by Aravax and underway in Australia, testing a novel treatment using carefully selected peanut protein fragments to switch off allergic reactions.

"If we can identify the key peanut protein fragment recognized by an individual’s immune response, we can determine whether that patient will experience less of a side effect from that therapy," Dr.  Kwok said. 

According to Dr. Wambre, "The goal is to follow patients currently receiving treatment to look at the differences in immune response between groups of patients, and understand how that response correlates with treatment effectiveness and side effects that the patients experience."

What they discover could guide the design of a new strategy for immune intervention and provide a framework for applying precision medicine in peanut allergy. This study will also allow researchers to identify whether there are differences between children and adults receiving the same kind of therapy for peanut allergy. 

 "This will be the first demonstration that peanut allergy may no longer be considered a single entity with a ‘one size fits all’ approach to treatment," states Peter Linsley, PhD, the third BRI collaborator who leads the­­­­ data science core that serves as the bridge between the two parts of the study. His team provides state-of-the-art technology and data analytics, incorporating BRI’s tetramer tool, developed by Dr. Kwok, and single cell transcription, which allows researchers to isolate cells that recognize peanut protein. Those cells’ qualities are then analyzed by Linsley’s team.

Benaroya Research Institute scientists have been involved in several major food allergy-related discoveries in the last couple years. These include BRI’s 2017 TH2A allergy cell discovery and the 2016 Immune Tolerance Network-sponsored LEAP clinical trial to prevent peanut allergy in children. Also, Drs. Kwok, Wambre and Robinson have teamed up to publish at least 16 papers in the area of allergy. Since 2016, Virginia Mason and BRI have been members of the Food Allergy Research and Education (FARE) Clinical Network.

Discovery could accelerate research toward better ways to diagnose, monitor and treat allergies that affect millions.

Scientists at the Benaroya Research Institute at Virginia Mason (BRI) have made a discovery that could change the trajectory of allergy research, by identifying a single type of cell that appears to drive all allergies. This cell, called Th2A, could be a promising focal point for research to improve diagnosis, monitoring and treatment of allergies. Additionally, these cells could be used as biomarkers, or indicators that show whether a person has an allergy or is responding to therapy. The research was published in the latest issue of Science Translational Medicine.

Virginia Mason and its affiliate Benaroya Research Institute (BRI) are among the newest members of the Food Allergy Research & Education (FARE) network, a leading nonprofit organization working on behalf of the 15 million Americans with food allergies.

FARE announced its expansion today to now include Virginia Mason and Benaroya Research Institute; Columbia University Medical Center and NewYork-Presbyterian/Morgan Stanley Children’s Hospital in New York; Gores Family Allergy Center at Children’s Hospital Los Angeles; ‘Specially for Children, an affiliate of Dell Children’s Medical Center of Central Texas, an Ascension hospital in Austin; and University of Utah Health Care/Primary Children’s Hospital in Salt Lake City.

“We’re honored to have been selected to participate in the important work the FARE network is leading to improve safety and quality of life for individuals coping with food allergies,” said David Jeong, MD, a food allergy researcher and section head for allergy and immunology at Virginia Mason. “We are eager to collaborate with other centers of excellence across the nation to address this health issue through clinical research and discovery.”

“We’re delighted to join the FARE network to accelerate the development of life-saving diagnosis and treatment for people suffering with food allergies,” says BRI President Jane Buckner, MD. “In partnership with Virginia Mason clinicians, we’re increasing scientific knowledge about how allergies occur and pioneering the development of biomarkers for diagnosis, patient monitoring and prognosis in allergies. We’re honored to be counted among leaders in food allergy research, translating research in the laboratory to the clinic and back again.”

Launched in 2015, the FARE Clinical Network strives to accelerate the development of drugs for patients with food allergies as well as improve the quality of care for this serious illness. The network is made up of 28 leading research and care sites nationwide and represents an investment by FARE of approximately $2.7 million annually. In approximately one year, FARE Clinical Network centers served more than 56,000 patients with food allergies, with more than one-third of those patients new to the centers, reinforcing the urgent need for initiatives such as the network. FARE Clinical Network, an initiative that aims to accelerate the development of drugs for patients with food allergies as well as improve the quality of care for this serious illness.

Food allergy, the abnormal response to a food triggered by the body’s immune system, affects an estimated 6 to 8 percent of children under age 3 and up to 3 percent of adults, according to The Mayo Clinic.

“Accelerating the pace of research on food allergies and helping to ensure that we can expand access to clinical trials and high-quality medical care is one of FARE’s top priorities,” said James R. Baker, Jr., MD, CEO and chief medical officer of FARE. “The addition of five exemplary institutions to the FARE Clinical Network enables FARE to significantly broaden the reach of this initiative.”

FARE Clinical Network centers serve as sites for clinical trials for development of therapeutics and best practices for the care of patients with food allergies. The FARE Clinical Network is a powerful driver of collaboration to advance the field of food allergy, with member centers contributing to the development of a national food allergy patient registry. FARE plans to further expand the network to 40 to 50 sites within the next three years.

Members of the FARE Clinical Network are selected through a comprehensive, rigorous application process. The centers of excellence selected as part of the FARE Clinical Network provide high-quality clinical and sub-specialty food allergy expertise and services, and are focused on applying new evidence-based knowledge to this important field. These centers also meet high standards for clinical care, teaching and clinical research. View the full list of FARE centers of excellence.

“The FARE Clinical Network is a brilliant way to jump-start regional food allergy centers,” said Stephen Tilles, MD, a member of the FARE Clinical Advisory Board Executive Committee. “In our case at the Northwest Asthma and Allergy Center in Seattle and at centers across the country, FARE has provided funding that is critically needed in order to maintain a high quality food allergy center, contributing toward the acceleration of food allergy research and the availability of new treatments for patients. FARE support offsets costs for research coordinators who help manage the process of complex clinical trials, facilitating access to these trials for the patient community.”

In adults, foods that most often trigger allergic reactions include fish, shellfish, peanuts, and tree nuts, such as walnuts. Problem foods for children can include eggs, milk, peanuts, tree nuts, soy, and wheat, according to the National Institutes of Health. The allergic reaction may be mild. In rare cases it causes a potentially life-threatening reaction called anaphylaxis. Symptoms of food allergy may include itching or swelling in the mouth; vomiting, diarrhea, or abdominal cramps and pain; hives or eczema; tightening of the throat and trouble breathing; and/or drop in blood pressure. FARE recommends individuals managing food allergies meet with their physicians to discuss their individual needs in order to inform their personal healthcare decisions.

About Virginia Mason Health System
Virginia Mason, founded in 1920, is a nonprofit regional health care system based in Seattle that serves the Pacific Northwest. In the Puget Sound region, the system includes 336-bed Virginia Mason Hospital; a primary and specialty care group practice of more than 500 physicians; regional medical centers in Seattle, Bainbridge Island, Bellevue, Federal Way, Kirkland, Issaquah and Lynnwood; Bailey-Boushay House, the first skilled-nursing and outpatient chronic care management program in the U.S. designed and built specifically to meet the needs of people with HIV/AIDS; Benaroya Research Institute, which is internationally recognized for autoimmune disease research; and Virginia Mason Institute, which trains health care professionals and others from around the world in the Virginia Mason Production System, an innovative management methodology for continually improving quality, safety and efficiency. Virginia Mason online: VirginiaMason.org

Virginia Mason also includes Yakima-based Memorial Family of Services and Yakima Valley Memorial Hospital, a 226-bed facility serving the Yakima Valley in Central Washington since 1950. Memorial Family of Services comprises primary care practices and specialty care services, including high quality cardiac care, a continuum of cancer care, hospice care, and advanced services for children with special health care needs. Memorial online: YakimaMemorial.org

Erik Wambre, PhD, an immunology and allergy researcher at Benaroya Research Institute at Virginia Mason (BRI), has received a Mid-Career Investigators Award from Food Allergy Research & Education (FARE) that provides $750,000 over five years to support research in food allergy, specifically peanut allergy.

Wambre will identify and isolate the T cells that cause peanut allergy. The genes used by these T cells will be studied to understand why these cells are causing allergies. This information will then be used to discover how to effectively neutralize these cells and cure peanut allergy. The FARE award contributes to the pioneering work at BRI to better understand the immune system’s response to allergies and develop new approaches for diagnosis and treatment.

“BRI’s allergy program is a leading innovator in the development of biomarkers for diagnosis, patient monitoring and prognosis,” said Gerald Nepom, MD, PhD, director, BRI. “Our work shows for the first time precisely what immune cells ‘see’ when they respond to allergens and measures precisely how this occurs. This is an important advance for allergy research and patient care.”

The work is being conducted in collaboration with physicians of the Virginia Mason Department of Asthma, Allergy and Immunology. David Jeong, MD serves as the lead clinical researcher along with physicians Mary Farrington and David Robinson, who all provide clinical expertise and data from a group of clinical research volunteers.

“The breadth of research from the laboratory, translated into clinical treatment and back to the laboratory is really all under ‘one roof’ here,” said Dr. Nepom, “forming a dynamic collaboration to find the best treatments for people with allergic disease.”

Errors made by the body’s immune system initiate allergies, Wambre explained. “The immune system of individuals who are allergic to allergens such as peanuts or pollen is induced by immune cells called T cells to respond in ways which cause inflammation and allergy symptoms,” he added.

“Using a technology pipeline developed at BRI, we can now trace the T cells that cause allergy,” Wambre said. “The genes used by these T cells will be analyzed to find out why these cells are causing allergies. Then this information will be used to improve strategies to neutralize these cells and treat allergies. This work has already successfully developed practical tools to study allergies in molecular detail, providing new insights into therapeutic targets.”

William Kwok, PhD, co-investigator with Wambre, initiated BRI’s studies in allergy almost a decade ago. Other BRI experts involved in allergy research represent systems immunology; bioinformatics, genomic, bioregistries and clinical cores.

More than 50 million people in the U.S., or more than 1 in 5 individuals, suffer from all types of allergies, including indoor/outdoor, food and drug, latex, insect, skin and eye allergies. Allergy prevalence overall has been increasing since the early 1980s. For some individuals, allergies not only compromise quality of life but can be life-threatening.

FARE is the world’s largest private source of funding for food allergy research. Learn more about FARE online.

Scientists at Benaroya Research Institute at Virginia Mason (BRI) recently received a $2.2 million grant from the National Institutes of Health to find a unique biomarker that initiates and drives allergies. This grant expands on previous discoveries that led to the isolation of a type of white blood cells that show up only in people with allergic disease. 

“We hope to identify a biomarker at the top of the allergic chain reaction that will predict the onset of allergy and will lead to novel vaccine approaches,” says Erik Wambre, PhD, BRI Principal Investigator for the grant. “Our aim is to develop a simple blood test to predict the likelihood of resolution of an allergy during therapy and to identify people who will develop an allergy before the first symptoms are experienced. This is especially important in at-risk people such as children with a life-threatening food allergy.”

BRI investigators will focus on a specific white blood cell, a rare type of T cell, identified in earlier work by Dr. Wambre as a key initiator of the allergic response. T cells are a part of the immune system that orchestrate immune response and that generally protect the body from bacteria, viruses and parasites. But sometimes T cells make mistakes that harm the body such as attacking tissues causing autoimmune diseases or overacting to a foreign substance (an allergen) such as food, pollen or animal dander that in most people is generally harmless. People react to the proteins in these allergens with an antibody that releases chemicals that cause sneezing; itching in the nose, eyes and ears; and in rare cases the life-threatening reaction anaphylaxis.

Allergies are probably the most common immune disease in the industrialized world, affecting about 50 million people in the U.S. and 60 million people in Europe. It is estimated that by 2050 about one in two people will have allergies. These diseases represent a major public health concern in terms of quality of life, drug-related costs or even mortality. The reason for the increase in allergies isn’t known but modern living seems somehow to make people’s immune systems overly sensitive.

“Allergen-specific immunotherapy is currently the only curative treatment in allergies and has been used for the past 100 years,” says Dr. Wambre. “However, this approach doesn’t always work, is only limited to a few allergens at a time and it can take two to five years to build up immunity. Part of the reason for this is that researchers still don’t fully understand the precise mechanism of how allergies work in the body. Until now, there has been no biological measurement to predict who is likely to have these diseases until the development of clinical symptoms. Currently, physicians diagnose allergies based on clinical history and measurement of specific antibodies and skin reactivity to an allergen. However, the diagnosis may not be correct because of the number of variables involved. If we can identify the biomarkers at the beginning of the allergic chain reaction we can get ahead of the symptoms and try to find a therapy that will eliminate the allergy at the first step.”

Benaroya Research Institute at Virginia Mason (BRI) recently received a grant to research how blocking a particular molecule in metastatic breast cancer reduces both the growth of primary tumors and the number of lung metastases. BRI scientists have found in models of the disease that blocking this protein can shrink tumors by 60 - 80 percent and can keep the tumor from metastasizing or spreading to the lung. The $1.8 million five-year grant comes from the National Cancer Institute of the National Institutes of Health.

“We are excited to pursue this area of cancer research that links tumor growth to the type of immune system molecules that my laboratory has focused on for many years,” said the Principal Investigator of the grant, Steven F. Ziegler, PhD, Director of the Immunology Program at BRI. “We are looking at ways to block this protein in model systems that could be translated to humans. The goal of this work is to help develop a therapy to reduce primary breast cancer tumors, as well as the spread of this cancer to other areas. We also plan to study this in pancreatic and lung cancer as well because this protein plays a role in these diseases.”

In a study of the protein, Thymic Stromal Lymphopoietin (TSLP), in allergic responses Dr. Ziegler and his team used lung cancer as a “negative control group” and surprisingly found very high levels of the protein in people with lung tumors. In 2005, Dr. Ziegler and his colleagues discovered that TSLP was instrumental in initiating the inflammatory cascade that leads to the development of asthma and other allergic diseases. Since then, the researchers also found TSLP to be critical in other immune system diseases. Dr. Ziegler has studied TSLP since 1993 and has developed many tools and strategies for studying the protein.

BRI researchers will test several ways to block TSLP to evaluate potential for treatments to help eliminate the cancer. “We will assess the utility of measuring TSLP to inform prognosis and how this might indicate whether more specific treatment plans may be necessary in some cases,” said Dr. Ziegler. His team also will be studying the protein versican that has been shown to turn on TSLP in tumor metastasis. Thomas Wight, PhD, BRI Director of the Matrix Biology Program, and a leading researcher of versican, will be a collaborator on the grant along with Scott Adams, PhD, Professor of Oncology, Department of Immunology at Roswell Park Cancer Institute. Emma Kuan, PhD, a postdoctoral fellow in Dr. Ziegler’s laboratory, is a major contributor and researcher on the grant.