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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.