Researchers Share Promising Research on Immunotolerance for Preventing Peanut Allergy
MARCH 07, 2018
W. Todd Penberthy
Talal A. Chatila, MD, PhDOther than dietary avoidance, there is no US Food and Drug Administration (FDA)-approved therapy that can eliminate or cure food allergies. At Monday’s plenary 2018 American Academy of Allergy, Asthma & Immunology (AAAAI) Congress lecture, 3 pioneers in their field presented the latest research elucidating the understanding of food tolerance, and how this may be eliminated in the future.
They also shared latest advances in food allergy molecular diagnostics, and the latest clinical trials.
Animal models of human disease research are always decades ahead of clinical research in the understanding of pathogenic mechanisms with consideration of potential targets to effectively treat disease. Professor Talal A. Chatila, MD, PhD, in the Department of Immunology, Harvard University, presented extensive basic science research using mouse models of food allergy.
Analysis of bacterial species diversity in children with peanut allergies performed every 6 months for 30 months led to the characterization of particular bacterial strains of interest. Chatila and investigators demonstrated that they could eliminate peanut allergy in mice that previously had peanut allergies, by first treating with an antibiotic and subsequently introducing particular microbiome. Chatila stated that therapies targeting microbiota may enable the establishment of long-term tolerance.
While food extracts have commonly been used in the past, great strides have been made in identifying food allergens at the molecular level. Motohiro Ebisawa, MD, PhD, President-elect of World Allergy Organization (WAO), presented the latest advances in molecular food allergy diagnostics.
Ebisawa presented many different identified food allergens categorized into families of proteins — seed storage proteins, pollen related, peach-related, and cross-reactive carbohydrate determinant protein categories to name just a few. With an extract, clinicians may consider many proteins, but with individual molecules, clinicians can garner greater clinical insight into the individual’s food allergy.
Ebisawa reviewed research into the allergens specific for hazelnut, soy, walnut, cashew, and sesame, stressing that use of allergen components resolved diagnostics is rapidly evolving and increases the possibility to manage food allergic patients with a more individual approach.
Next, Stacie Jones, MD, Professor of Pediatrics and Chief of Allergy and Immunology at the Arkansas Children's Hospital and researcher at the Arkansas Children's Hospital Research Institute, presented her research on “Cutting Edge-food Allergy Pathogenesis, Diagnosis, and Therapy.”
Jones presented her research on 2 therapies designated by the FDA as fast-track breakthrough therapies: oral immunotolerance (OIT) AR101 and epicutaneous immunotolerance (EPIT) Viaskin peanut.
AR101 is a proprietary powder that is administered at escalating doses up to 9 months before a maintenance dose is achieved. The individual then undergoes a cautious food challenge at the prepared hospital settings in clinical studies. Multiple randomized, controlled trials have demonstrated that AR101 was effective at promoting desensitization.
Most impressive of all, unresponsiveness to peanut allergen was observed in a subpopulation of another study after 4 weeks of halting therapy.
The other fast-tracked product under investigation covered by Jones was the Viaskin peanut skin patch. It works by providing peanut antigen to dendritic cells which deliver the antigen to lymph nodes, from where T-regulatory cells are altered to confer some level of peanut tolerance.
In the COFAR6 clinical study (n=75) 100µg of Viaskin peanut patch was compared to placebo. Patients were subjected to 5g oral food challenge after treatment. Successful consumption of 5g peanut powder was observed for 10% for placebo, 46% of 100 µg patch, and 48% of 200 µg patch. VIPES and PEPITES clinical trials were also just completed and the data was presented as well.
In summary, Jones emphasized that oral immunotherapy appears to be particularly promising and has strong potential for anaphylaxis protection when administered by the protocol. Sublingual immunotherapy is in the clinical research pipeline and more work in biomarkers is needed to better assess and characterize treatment response and enhance safety predictability.
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