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Clinical Trial
. 2025 Feb;155(2):650-655.
doi: 10.1016/j.jaci.2024.10.033. Epub 2024 Nov 10.

Low-dose IL-2 in birch pollen allergy: A phase-2 randomized double-blind placebo-controlled trial

Michelle Rosenzwajg  1 , Alina Gherasim  2 , Franck Dietsch  2 , Marine Beck  2 , Nathalie Domis  2 , Roberta Lorenzon  1 , Yannick Chantran  3 , Bertrand Bellier  4 , Eric Vicaut  5 , Angele Soria  6 , Frederic de Blay  2 , David Klatzmann  7
Affiliations
Clinical Trial

Low-dose IL-2 in birch pollen allergy: A phase-2 randomized double-blind placebo-controlled trial

Michelle Rosenzwajg et al. J Allergy Clin Immunol. 2025 Feb.

Abstract

Background: Regulatory T (Treg) cells are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2LD) activates Treg cells.

Objective: Our aim was to assess IL-2LD efficacy for controlling clinical responses to allergen exposures.

Methods: RHINIL-2 was a phase-2a, randomized, double-blind, placebo-controlled trial. Patients with allergic rhinitis to birch pollen (BP) were included; 66% of them had concomitant asthma. All had a total nasal symptom score (TNSS) of 5 or more following nasal exposure to BP in an environmental exposure chamber. Patients received 1 MUI per day of IL-2 (n = 12) or placebo (n = 12) for 5 days, followed by weekly injections for 4 weeks. Clinical responses to subsequent BP exposures in the environmental exposure chamber were evaluated by using TNSS, the rhinitis visual analog scale (VAS), and spirometry. The primary efficacy end point was the difference in TNSS area under the curve (AUC) between inclusion and day 40.

Results: IL-2LD treatment induced a significant expansion of Treg cells. The difference in TNSS AUC between inclusion and day 40 AUC in the IL-2 and placebo groups was not significant. TNSS and visual analog scale AUCs were significantly reduced from baseline to day 40 in the IL-2LD group only (P = .04 and P = .01, respectively). The ratio of FEV1 to forced vital capacity (FEV1P) and the forced midexpiratory flow (FEF25%-75%) showed improvement in the IL-2LD-treated versus in the groups given placebo at day 40 (P = .04 and P = .04, respectively). However, the short treatment duration used in this study could not have effects on specific IgE or IgG4 levels given their half-life. There were no severe treatment-related adverse events.

Conclusion: IL-2LD is well tolerated in patients with allergy, even in those with asthma, thus clearing the path for further therapeutic development. Our work suggests that Treg cells can safely attenuate an ongoing allergic response. It paves the way for larger studies with longer treatment periods, which are needed to properly evaluate the therapeutic potential of IL-2 in allergy.

Keywords: Tolerance; biotherapy; immunopathologies; immunotherapy.

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Conflict of interest statement

Disclosure statement Supported by the Programme Hospitalier de Recherche Clinique, No. P160936J. The Assistance Publique-Hôpitaux de Paris sponsored the study, and ILTOO pharma provided the treatments. Disclosure of potential conflict of interest: M. Rosenzwajg, R. Lorenzon, B. Bellier, and D. Klatzmann are inventors on patent applications related to the therapeutic use of IL-2(LD), which belongs to their academic institutions and has been licensed to ILTOO Pharma. M. Rosenzwajg, B. Bellier, and D. Klatzmann hold shares in ILTOO Pharma. The rest of the authors declare that they have no relevant conflicts of interest.

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