Phase 1 trial supports safety and mechanism of action of peptide immunotherapy for peanut allergy.

Autor: Voskamp AL; Aravax Pty Ltd, Melbourne, Victoria, Australia.; Monash University, Melbourne, Victoria, Australia.; Alfred Health, Melbourne, Victoria, Australia.; WhiteFox Science Consulting, Nelson, New Zealand., Khosa S; Benaroya Research Institute, Seattle, Washington, USA., Phan T; Aravax Pty Ltd, Melbourne, Victoria, Australia.; Monash University, Melbourne, Victoria, Australia.; Alfred Health, Melbourne, Victoria, Australia., DeBerg HA; Benaroya Research Institute, Seattle, Washington, USA., Bingham J; Aravax Pty Ltd, Melbourne, Victoria, Australia.; Easington Pty Ltd, Melbourne, Victoria, Australia., Hew M; Monash University, Melbourne, Victoria, Australia.; Alfred Health, Melbourne, Victoria, Australia., Smith W; AllergySA, Adelaide, South Australia, Australia., Abramovitch J; Monash University, Melbourne, Victoria, Australia.; Alfred Health, Melbourne, Victoria, Australia., Rolland JM; Monash University, Melbourne, Victoria, Australia., Moyle M; Aravax Pty Ltd, Melbourne, Victoria, Australia., Nadeau KC; Stanford University, San Francisco, California, USA., Lack G; Kings College, London, UK., Larché M; Schroeder Allergy & Immunology Research Institute, Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada., Wambre E; Benaroya Research Institute, Seattle, Washington, USA., O'Hehir RE; Aravax Pty Ltd, Melbourne, Victoria, Australia.; Monash University, Melbourne, Victoria, Australia.; Alfred Health, Melbourne, Victoria, Australia., Hickey P; Aravax Pty Ltd, Melbourne, Victoria, Australia., Prickett SR; Aravax Pty Ltd, Melbourne, Victoria, Australia.; Monash University, Melbourne, Victoria, Australia.; Alfred Health, Melbourne, Victoria, Australia.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2024 Feb; Vol. 79 (2), pp. 485-498. Date of Electronic Publication: 2023 Dec 19.
DOI: 10.1111/all.15966
Abstrakt: Background: Food allergy is a leading cause of anaphylaxis worldwide. Allergen-specific immunotherapy is the only treatment shown to modify the natural history of allergic disease, but application to food allergy has been hindered by risk of severe allergic reactions and short-lived efficacy. Allergen-derived peptides could provide a solution. PVX108 comprises seven short peptides representing immunodominant T-cell epitopes of major peanut allergens for treatment of peanut allergy.
Methods: Pre-clinical safety of PVX108 was assessed using ex vivo basophil activation tests (n = 185). Clinical safety and tolerability of single and repeat PVX108 doses were evaluated in a first-in-human, randomized, double-blind, placebo-controlled trial in peanut-allergic adults (46 active, 21 placebo). The repeat-dose cohort received six doses over 16 weeks with safety monitored to 21 weeks. Exploratory immunological analyses were performed at pre-dose, Week 21 and Month 18 after treatment.
Results: PVX108 induced negligible activation of peanut-sensitised basophils. PVX108 was safe and well tolerated in peanut-allergic adults. There were no treatment-related hypersensitivity events or AEs of clinical concern. The only events occurring more frequently in active than placebo were mild injection site reactions. Exploratory immunological analyses revealed a decrease in the ratio of ST2 + Th2A:CCR6 + Th17-like cells within the peanut-reactive Th pool which strengthened following treatment.
Conclusion: This study supports the concept that PVX108 could provide a safe alternative to whole peanut immunotherapies and provides evidence of durable peanut-specific T-cell modulation. Translation of these findings to clinical efficacy in ongoing Phase 2 trials would provide important proof-of-concept for using peptides to treat food allergy.
(© 2023 Aravax Pty Ltd. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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