Immune Tolerance in Allergy & Asthma

Allergy and asthma are intertwined in many ways. Allergies during infancy often precede the development of asthma. Additionally, Allergies can worsen asthma and induce an attack. Allergies occur when the body's immune system over-reacts to a more or less harmless substance. Food and drug allergies can be particularly dangerous, as they can often cause anaphylaxis, a rapid and severe reaction that can lead to shock.

The available treatments for allergies are varied and only relieve symptoms without curing the underlying problem. A technique called "allergen immunotherapy," where regular, repeated administration of the allergen over a long period of time, done under the supervision of physicians, can induce desensitization for some allergies. Unfortunately, while it has been confirmed to work for certain airborne allergens, it has not been proven to be permanent.

The Immune Tolerance Network (ITN) is seeking to develop new, improved methods of combating allergy and asthma that will be durable while requiring a much shorter treatment period, with higher rates of success than conventional immunotherapy. The ITN is also interested in finding ways to prevent the development of allergies, and the asthma that often results, in young children.

Research Focus - Allergy & Asthma

The ITN’s portfolio has focused on modifying validated desensitization protocols to induce durable tolerance. These studies were designed to test whether allergens could induce tolerance by altering the allergen structure, the timing of administration or the route of administration, and whether early allergen introduction in at-risk children could prevent future allergies. The ITN is currently developing novel trials to advance desensitization to true tolerance by focusing on combination therapies that administer allergen in the context of an immune modifying therapy (called “allergen plus”). The goal is to target known allergic pathways in a manner that will facilitate non-inflammatory recognition and processing of antigens to enhance the efficacy and safety of immunotherapy. The ITN will also continue to explore new allergen preparations and routes of administration to maximize the effectiveness of true tolerogenic protocols.

The ITN is also pioneering the in vitro definition of allergen-specific tolerance. As part of this effort the ITN has initiated a set of pilot studies to map detailed, time-dependent immune responses to allergen immunotherapy, as well as to refine methodologies for optimal specimen collection and processing.  The goal is to use this information to design treatment regimens and clinical studies that better target allergic pathways and promote tolerance. 

Clinical Trials - Allergy & Asthma

Active

Oral Immunotherapy for Induction of Tolerance and Desensitization in Peanut-Allergic Children (IMPACT)

Protocol Chair:
Wesley Burks, MD │ UNC Chapel Hill │ Chapel Hill, NC

IMPACT is a clinical research study testing whether daily oral exposure to a peanut product can modify peanut allergy in young children.

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Persistence of Oral Tolerance to Peanut (LEAP-ON)

Protocol Chair:
Gideon Lack, MD , Evelina Children's Hospital , London, UK

This is a follow-on study to the ITN’s LEAP trial to evaluate the persistence of tolerance to peanut, and whether continued consumption of peanuts throughout life is required in order to be able to safely eat peanuts without reacting.

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Long-Term Effects of Sublingual Grass Therapy (GRASS)

Protocol Chair:
Stephen Durham, MD, Imperial College, London, United Kingdom

GRASS is a clinical research study looking at long-term immunity from the symptoms of hay fever. The study is testing the effectiveness of two commercially available tolerance-increasing treatments.

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Promoting Tolerance to Peanut in High-Risk Children (LEAP)

Protocol Chair:
Gideon Lack, Evelina Children's Hospital, London, United Kingdom

Infants who suffer from eczema or egg allergy have a 1 in 5 chance of developing peanut allergy by age 5. This study is evaluating whether consuming or avoiding peanut early in life can reduce the risk of peanut allergy in these high risk children.

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Completed

Promoting Tolerance to Common Allergens in High-Risk Children: Global Prevention of Asthma in Children (GPAC) Study

Protocol Chair:
Patrick Holt, University of Western Australia, Perth, AUS

Peter Sly, Telethon Institute for Child Health Research, Perth, AUS

The purpose of this study is to determine whether early childhood exposure to common allergens (substances that can trigger allergies and asthma) can prevent the development of asthma in children at high risk for developing the disease.

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Allergen ISS Conjugates in Allergic Rhinitis

Protocol Chair:
Peter Creticos, Johns Hopkins University, Baltimore, MD

This study will evaluate the effectiveness of a six-week course of a DNA-based vaccine for seasonal allergic rhinitis, also known as hayfever.

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Efficacy and Safety Evaluation of Allergen Immunotherapy Co-Administered with Omalizumab, an anti-IgE Monoclonal Antibody

Protocol Chair:
Thomas B. Casale, Creighton University School of Medicine, Omaha, NE

A series of allergy shots may reduce symptoms of seasonal ragweed allergies. This study will determine whether taking a drug called omalizumab (also known as Xolair) before getting the allergy shots is more effective than allergy shots alone or other treatments, such as prescription antihistamines.

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