Production of allergen-specific immunotherapeutic agents for the treatment of food allergy

Abstract

Allergen-specific immunotherapy (IT) is emerging as a viable avenue for the treatment of food allergies. Clinical trials currently investigate raw or slightly processed foods as therapeutic agents, as trials using food-grade agents can be performed without the strict regulations to which conventional drugs are subjected. However, this limits the ability of standardization and may affect clinical trial outcomes and reproducibility. Herein, we provide an overview of methods used in the production of immunotherapeutic agents for the treatment of food allergies, including processed foods, allergen extracts, recombinant allergens, and synthetic peptides, as well as the physical and chemical processes for the reduction of protein allergenicity. Commercial interests currently favor producing standardized drug-grade allergen extracts for therapeutic use, and clinical trials are ongoing. In the near future, recombinant production could replace purification strategies since it allows the manufacturing of pure, native allergens or sequence-modified allergens with reduced allergenicity. A recurring issue within this field is the inadequate reporting of production procedures, quality control, product physicochemical characteristics, allergenicity, and immunological properties. This information is of vital importance in assessing therapeutic standardization and clinical safety profile, which are central parameters for the development of future therapeutic agents.

Keywords:

• Food allergy
• immunotherapy
• extracts
• recombinant production
• food processing
• synthetic peptides

Author contributions

KLB and JU conceived the review topic. JML, KLB, CHBB and KQ outlined the manuscript draft. JML drafted the abstract, introduction, IT evaluation, and conclusion sections, and sections on whole, cooked and processed food. AIS drafted the sections on extracts and purified allergens. CHBB, KIHA, and SSNT drafted the section on recombinant allergens and peptides. KQ and AHH drafted the sections on synthetic peptides, allergoids, and hydrolysis. JML edited the final draft. All authors have made substantial intellectual contributions and revised the manuscript critically. All authors reviewed and approved the final version of the manuscript, and agreed to be accountable for all aspects of the work.

Disclosure statement

JU is and has been an investigator for Regeneron, DBV Technologies and Aimmune Therapeutics, and investigator lead OIT studies funded by SickKids foundation. TE is an investigator for Regeneron and DBV Technologies, and investigator lead OIT studies funded by SickKids foundation. The remaining authors declare no competing interest in regard to the publication of this manuscript.

Additional information

Funding

This work is part of the ALLEVIATE project funded by Innovation Fund Denmark [grant number 6159-00005B]. KQ and AHH were additionally supported by the Novo Nordisk Foundation. The foundations had no involvement in the preparation of the manuscript or decision to publish.