CLINICAL TRIAL article
Front. Immunol.
Sec. Immunological Tolerance and Regulation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1655975
This article is part of the Research TopicExploring Immunological Tolerance in Allergy Treatment through AITView all 15 articles
Trends in allergen-reactive CRTH2+ T cells and TARC associated with successful outcomes in a Phase 2 Cashew Oral Immunotherapy study
Provisionally accepted
Sayantani B Sindher1
Andrea Fernandes1
Monali Manohar1
Shu Cao1
Sheena Gupta1
Ella Parsons1Dinara Bogetic1
Divya Kumar1Jessica Rogers1Julia Thompson1Diane Dunham1Evan Do1Sofia Maysel-Auslender1Taryn Audrey Liu1Kristine Martinez1
Brent Anderson1
Abhinav Kaushik2Manisha Desai1
Holden Maecker1Susan Perry3Lisa M Wheatley3
Kari Nadeau2*
R. Sharon Chinthrajah1- 1Stanford University, Stanford, United States
- 2Department of Environmental Health, School of Public Health, Harvard University, Boston, United States
- 3National Institutes of Health, Bethesda, United States
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Background: We designed an oral immunotherapy (OIT) clinical trial for cashew allergy to further our understanding of immunological responses with treatment, including changes in allergen-specific T cells. This information can further assist with the design of efficacious and safe treatments. Methods: Participants were built up to and maintained on 1 g of cashew flour protein. Double-blind, placebo-controlled food challenges (DBPCFCs) were conducted before and after dosing completion (week 52) and 6 weeks after dosing discontinuation (week 58). Desensitization (DS) and sustained unresponsiveness (SU) were defined as tolerating DBPCFC to a cumulative dose of 2043 mg of the allergen at weeks 52 and 58, respectively. ClinicalTrials.gov, number NCT03504774. Results: We enrolled 40 cashew allergic participants. In the Intent-to-treat (ITT) population, both the DS and SU rate to cashew was 65% (26/40). Among cashew-reactive cells, CRTH2+ CD4+ T cells decreased at week 52 and week 58 compared to baseline. Additionally, we also saw reduced baseline expression of cytokines TARC, EGF and IP10 among participants that achieved SU at 4043mg compared to those who achieved SU at 2043mg. Conclusion: Cashew OIT have efficacy and safety outcomes similar to other published OIT studies. Reductions in pathogenic allergen-specific T cell populations may contribute to the immune mechanisms underlying tolerance achieved towards cashew post-treatment.
Keywords: food allergy, oral immunotherapy, Allergen-specific T cells, Cashew allergy, tolerance
Received: 29 Jun 2025; Accepted: 17 Sep 2025.
Copyright: © 2025 Sindher, Fernandes, Manohar, Cao, Gupta, Parsons, Bogetic, Kumar, Rogers, Thompson, Dunham, Do, Maysel-Auslender, Liu, Martinez, Anderson, Kaushik, Desai, Maecker, Perry, Wheatley, Nadeau and Chinthrajah. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kari Nadeau, knadeau@hsph.harvard.edu
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