Cracking peanut allergy with gene therapy

Published Online: June 29, 2016

Peanut allergy is a major public health problem that accounts for the majority of fatal food-induced anaphylactic reactions. There are no FDA-approved curative or preventative therapies, and strict avoidance of peanuts is the only accepted and effective management strategy. Peanut allergy is an IgE-mediated reaction that progresses rapidly after exposure to the allergen. Prior studies suggest that repeated doses of the drug omalizumab, which blocks immunoglobulin E (IgE), may provide short-term protection, but it must be administered frequently and is costly.  A novel gene therapy strategy using anti-hIgE antibodies has been established to allow for a single treatment providing long-lasting, life-saving therapeutic benefit.

In an article recently published by Pagovich and collegues in The Journal of Allergy and Clinical Immunology (JACI), investigated a unique treatment for peanut allergy using gene therapy. The gene therapy in this study uses AAVrh.10anti-hIgE, an adeno-associated virus (AAVrh.10) gene transfer vector expressing an anti-hIgE antibody. The team theorized that a single administration of the AAVrh.10 gene transfer vector expressing the anti-hIgE monoclonal antibody would provide persistent anti-hIgE expression to protect against repeated peanut exposure in a peanut allergic host. In order to test this hypothesis, the team developed a novel humanized mouse model of peanut allergy by injecting immune cells from peanut allergic individuals into the mice. When exposed to peanuts, these mice had an anaphylactic reaction similar to that seen in humans. The test of the therapy was to determine if a single administration of prophylactic or therapeutic AAVrh.10anti-hIgE protected the peanut allergic mice, even after repeated peanut exposure.

Strikingly, after peanut challenge, AAVrh.10anti-hIgE-treated mice no longer displayed a severe allergic phenotype compared to those that received the control vector. The gene therapy worked like a sponge to bind up excessive levels of IgE resulting in a lower anaphylaxis score, increased locomotor activity, and reduced levels of mediators critical for initiating the allergic cascade. Notably, mice treated with a single administration of omalizumab were only protected for 2 weeks, whereas mice treated with AAVrh.10anti-hIgE were protected for 5 weeks (the last time point evaluated in the study). Remarkably, the AAVrh.10anti-hIgE treated mice had a 90% survival rate at 40 days post treatment, whereas only 30% of mice treated with a single administration of omalizumab and 11% of the mice treated with the control vector survived at the same time point.  
 
The authors’ findings suggest that a single administration of an AAVrh.10anti-hIgE gene transfer vector could provide long term protection from anaphylaxis in peanut allergic individuals. This study is the first to demonstrate a gene therapy platform for treating severe, human-related peanut allergy. While additional clinical experience and follow-up is needed, these promising results suggest gene therapy could potentially change the clinical approach for a large number of individuals living with peanut allergy. Moreover, if gene therapy can successfully treat peanut allergy then it also could potentially be applied to a wide spectrum of IgE mediated disorders and offers the possibility of entirely new avenues to treat peanut and other allergies.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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