Epicutaneous immunotherapy protects cashew‐sensitized mice from anaphylaxis

Abstract

Background The prevalence of tree nut allergy has increased worldwide, and cashew has become one of the most common food allergens. More critically, cashew allergy is frequently associated with severe anaphylaxis. Despite the high medical need, no approved treatment is available and strict avoidance and preparedness for prompt treatment of allergic reactions are considered dual standard of care. In the meantime, Phase III study results suggest investigational epicutaneous immunotherapy (EPIT) may be a relevant and safe treatment for peanut allergy and may improve the quality of life for many peanut allergic children. Objective We aimed to evaluate the capacity of EPIT to provide protection against cashew‐induced anaphylaxis in a relevant mouse model. Methods The efficacy of EPIT was evaluated by applying patches containing cashew allergens to cashew‐sensitized mice. As negative control, sham mice received patches containing excipient. Following treatment, mice were challenged orally to cashew and anaphylactic symptoms, as well as plasmatic levels of mast‐cell proteases (mMCP)‐1/7, were quantified. Results Of 16 weeks of EPIT significantly protects against anaphylaxis by promoting a faster recovery of challenged mice. This protection was characterized by a significant reduction of temperature drop and clinical symptoms, 60 minutes after challenge. This was associated with a decrease in mast‐cell reactivity as attested by the reduction of mMCP‐1/7 in plasma, suggesting that EPIT specifically decrease IgE‐mediated anaphylaxis. Conclusion We demonstrate that EPIT markedly reduced IgE‐mediated allergic reactions in a mouse model of cashew allergy, which suggests that EPIT may be a relevant approach to treating cashew allergy.

Comparative analysis of tropomyosin allergenicity in three different species of molluscs: insights into the role of amino acid composition in IgE epitopes

“…These findings were consistent with previous studies on TM and AK in mud crab, 11,12 which further supported the notion that HTM, ATM, and MTM were capable of inducing subsequent food allergy reactions through IgE production. As noted by Pelletier et al, 44 sIgE levels were used to determine the successful establishment of different mouse models. By the third injection, a significant difference in sIgE was observed, accompanied by elevated levels of IL-4.…”

“…19 Allergenicity refers to the ability of a food allergen to sensitize body and cause clinical symptoms after oral ingestion. 44 It is a measurement of the allergic response induced by allergens. In this study, the allergenicity of HTM, ATM, and MTM was likely evaluated by assessing the severity of allergic symptoms and the production of specific antibodies in the established mouse food allergy model.…”

An update on recent developments and highlights in food allergy

“…The follow‐up PEOPLE trial, a 2‐year open label extension of the PEPITES study, reported continued EPIT therapy remained clinically beneficial and tolerable, with an increase in eliciting dose from baseline 114 . EPIT continues to be investigated for various allergens including cashew, where EPIT recently demonstrated efficacy in reducing mast cell reactivity and anaphylactic symptoms in mouse models 115 . A range of different types of biomarkers are being utilized to mark the success of the various AIT administration routes (Table 1).…”

“…114 EPIT continues to be investigated for various allergens including cashew, where EPIT recently demonstrated efficacy in reducing mast cell reactivity and anaphylactic symptoms in mouse models. 115 A range of different types of biomarkers are being utilized to mark the success of the various AIT administration routes (Table 1).…”

Mechanisms and biomarkers of successful allergen-specific immunotherapy

“…Recently, epicutaneous immunotherapy (EPIT) received increased interest after a trial performed by Senti et al [ 28 ] in 2009, which suggested that EPIT could become a promising method for allergic diseases. EPIT involves the application of a noninvasive and painless patch containing an allergen extract to the skin, which avoids the ingestion of oral allergens improving the safety profile [ 29 30 31 ].…”