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.

Grass Pollen Immunotherapy Plus Dupilumab For Tolerance Induction (GRADUATE)

Principal Investigator:

Stephen R. Durham, MD | Imperial College, London

GRADUATE is a clinical research trial, which will test whether a novel drug called Dupixent® given with grass pollen immunotherapy will help the immunotherapy work in a shorter treatment period and remain effective after the completion of treatment.

Category: 

Allergy & Asthma

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Specific Category: 

Hayfever

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Status: 

Active

Vaginal Microbiome Exposure and Immune Responses in C-section Infants (ACTIVATE)

Principal Investigator:

Hugh Sampson, MD | Icahn School of Medicine at Mount Sinai | New York

Jose Clemente, PhD | Icahn Institute for Genomics and Multiscale Biology | New York

ACTIVATE is a clinical trial investigating the impact of the infant microbiome on allergy development.

Category: 

Allergy & Asthma

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Specific Category: 

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Status: 

Active

Follow up of LEAP Participants and Their Families (LEAP Trio)

Principal Investigator:

Gideon Lack | Evelina Childrens Hospital | London, UK

LEAP Trio is a follow-up to the LEAP study of early peanut consumption. LEAP Trio will investigate the durability of tolerance to peanut allergen in LEAP participants at age 12, development of peanut allergy in younger siblings of LEAP participants, and parental characteristics that may impact development of food allergy.

Category: 

Allergy & Asthma

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Specific Category: 

Peanut Allergy

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Status: 

Active

Cat Pilot Study - Environmental Exposure Chamber (EEC) vs. Nasal Allergen Challenge (NAC) (CAT EEC Study)

Principal Investigator:

Stephen Durham, MD | Imperial College London | London, UK

Piyush Patal, MD | Inflamax Research | Ontario, Canada

The goal of the CAT EEC study is to directly compare allergic responses to cat by environmental exposure chamber vs. nasal allergen challenge to better understand and employ these methods as allergy evaluation tools in clinical trials.

Category: 

Allergy & Asthma

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Specific Category: 

Cat Allergy

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Status: 

Completed

Anti-TSLP Plus Antigen-Specific Immunotherapy For Induction Of Tolerance In Individuals With Cat Allergy (CATNIP)

Principal Investigator:

Jonathan Corren, MD | University of California, Los Angeles | Los Angeles, CA

CATNIP is a clinical research trial, which will test whether a novel therapeutic approach, cat immunotherapy combined with an investigational new drug called MEDI9929/AMG 157 (an anti-TSLP antibody being co-developed by Amgen and Medimmune) can lead to lasting tolerance to cat allergen. This study will implement the concept referred to as “allergen-plus,” which aims to enhance the disease-modifying mechanisms of allergen-specific immunotherapy by combining it with other anti-inflammatory or immune-modulating agents.

Category: 

Allergy & Asthma

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Specific Category: 

Cat Allergy

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Status: 

Completed

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

Principal Investigator:

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.

Category: 

Allergy & Asthma

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Specific Category: 

Peanut Allergy

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Status: 

Completed

Persistence of Oral Tolerance to Peanut (LEAP-ON)

Principal Investigator:

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.

Category: 

Allergy & Asthma

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Specific Category: 

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Status: 

Completed

Long-Term Effects of Sublingual Grass Therapy (GRASS)

Principal Investigator:

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.

Category: 

Allergy & Asthma

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Specific Category: 

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Status: 

Completed

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

Principal Investigator:

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.

Category: 

Allergy & Asthma

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Specific Category: 

Peanut Allergy

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Status: 

Completed

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

Principal Investigator:

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.

Category: 

Allergy & Asthma

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Specific Category: 

Asthma⠀

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Status: 

Completed

Allergen ISS Conjugates in Allergic Rhinitis

Principal Investigator:

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.

Category: 

Allergy & Asthma

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Specific Category: 

Ragweed Allergy

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Status: 

Completed

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

Principal Investigator:

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.

Category: 

Allergy & Asthma

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Specific Category: 

Ragweed Allergy

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Status: 

Completed

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