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Clinical Reviews in Allergy & Immunology

, Volume 55, Issue 2, pp 172–189 | Cite as

Enhancing the Safety and Efficacy of Food Allergy Immunotherapy: a Review of Adjunctive Therapies

  • Yamini V. Virkud
  • Julie Wang
  • Wayne G. Shreffler
Article

Abstract

Food allergy is a potentially life-threatening condition with no approved curative therapy. A number of food allergen immunotherapies are being investigated in phase II/III trials; however, these are limited in their ability to restore immune tolerance to food allergens and often result in high rates of allergic side effects, sometimes involving anaphylaxis, that may curtail their impact. A variety of adjunctive therapies have been developed in order to enhance the efficacy and/or improve the safety of food allergen immunotherapy through either shifting the immune response from a Th2 polarized response to a Th1 and regulatory T cell dominated response or by blocking downstream effects of the allergic inflammatory response by targeting IgE or mast cell mediators. Upstream therapies that shift towards a Th1/Treg response include toll-like receptor (TLR) 4 agonists (e.g., MPL and GLA), TLR9 agonists (CpG oligonucleotides), nanoparticles encapsulating peanut allergen (with and without adjuvants, such as CpG or rapamycin), Chinese herbal medicine (food allergy herbal formula (FAHF-2)), probiotics, and interferon-gamma. In contrast, anti-IgE therapies such as omalizumab, anti-histamines like ketotifen, and leukotriene receptor antagonists all target the downstream allergic response. Anti-IgE-based therapies appear to be furthest along with probiotics, Chinese herbal medicines, and TLR-4 agonists currently in early phase clinical trials. Meanwhile, nanoparticles represent an innovative delivery vehicle for immunotherapy that could improve both efficacy and decrease allergic side effects. Furthermore, other biologic therapies directed towards the allergic immune response are on the horizon. A number of factors will need to be evaluated in comparing these treatments, including ability to decrease allergic adverse events, safety of the adjunctive therapies themselves, effect on long-term sustained unresponsiveness, and cost. Further phenotyping of food allergy patients may be necessary to determine which ones respond best to each therapy. However, with so many promising adjunctive therapies, it appears likely that clinicians will have a variety of options to optimize the administration of food allergen immunotherapy. We provided a review of these methods, their influence on allergic adverse events, and utility in improving the immunomodulatory effects of food allergen immunotherapy.

Keywords

Food allergy Oral immunotherapy Immunotherapy Anti-IgE Omalizumab Nanoparticles Toll-like receptor agonists 

Abbreviations

IgE

Immunoglobulin E

TLR

Toll-like receptor

Th

T helper

CpG

Cytosine-phosphate-guanine

ISS

Immunostimulatory sequence

MPL

Monophosphoryl lipid A

GLA

Glucopyranosyl lipid A

OVA

Ovalbumin

mTOR

Mammalian target of rapamycin

FAHF-2

Food allergy herbal formula 2

LTRA

Leukotriene receptor antagonists

DBPCFC

Double-blind, placebo-controlled food challenge

Notes

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflict of interest.

Research Involving Human Participants and/or Animals

This review article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent

This review article does not contain any primary work involving human participants requiring informed consent.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Allergy and Immunology, Department of PediatricsMassachusetts General HospitalBostonUSA
  2. 2.Division of Allergy and Immunology, Department of PediatricsMount Sinai HospitalNew YorkUSA

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