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Ann Rheum Dis. 2019 Feb;78(2):209-217. doi: 10.1136/annrheumdis-2018-214229. Epub 2018 Nov 24.

Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial.

Author information

1
Inflammation-Immunopathology-Biotherapy Department (i2B), AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
2
Immunology-Immunopathology- Immunotherapy (i3), Sorbonne Université, INSERM, Paris, France.
3
Department of Internal Medicine and Clinical Immunology, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
4
ILTOO Pharma, Paris, France.
5
Department of Dermatology, AP-HP Cochin Hospital, Paris, France.
6
Department of Rheumatology, AP-HP Pitié-Salpêtrière Hospital, Paris, France.
7
Department of Gastroenterology, AP-HP Saint Antoine Hospital, Paris, France.
8
Department of Rheumatology, AP-HP Saint-Antoine Hospital, Paris, France.
9
Department of Hepatology, AP-HP Saint-Antoine Hospital, Paris, France.
10
Department of Internal Medicine, AP-HP, Saint-Antoine Hospital, Paris, France.
11
Department of Pharmacology and CIC-1421, AP-HP Pitié-Salpêtrière Hospital, Paris, France.
12
Department of Pharmacy, AP-HP Saint-Antoine Hospital, Paris, France.
13
Unité de Recherche Clinique and Université Paris, AP-HP Saint Louis/Lariboisière Hospitals, Paris, France.
14
Inflammation-Immunopathology-Biotherapy Department (i2B), AP-HP, Pitié-Salpêtrière Hospital, Paris, France david.klatzmann@sorbonne-universite.fr.
#
Contributed equally

Abstract

OBJECTIVE:

Regulatory T cells (Tregs) prevent autoimmunity and control inflammation. Consequently, any autoimmune or inflammatory disease reveals a Treg insufficiency. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential.

AIM:

We aimed to assess this potential and select diseases for further clinical development by cross-investigating the effects of ld-IL2 in a single clinical trial treating patients with 1 of 11 autoimmune diseases.

METHODS:

We performed a prospective, open-label, phase I-IIa study in 46 patients with a mild to moderate form of either rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Behcet's disease, granulomatosis with polyangiitis, Takayasu's disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis and sclerosing cholangitis. They all received ld-IL2 (1 million IU/day) for 5 days, followed by fortnightly injections for 6 months. Patients were evaluated by deep immunomonitoring and clinical evaluation.

RESULTS:

ld-IL2 was well tolerated whatever the disease and the concomitant treatments. Thorough supervised and unsupervised immunomonitoring demonstrated specific Treg expansion and activation in all patients, without effector T cell activation. Indication of potential clinical efficacy was observed.

CONCLUSION:

The dose of IL-2 and treatment scheme used selectively activate and expand Tregs and are safe across different diseases and concomitant treatments. This and preliminary indications of clinical efficacy should licence the launch of phase II efficacy trial of ld-IL2 in various autoimmune and inflammatory diseases.

TRIAL REGISTRATION NUMBER:

NCT01988506.

KEYWORDS:

biotherapy; immunopathologies; immunotherapy; systems biology; tolerance

Conflict of interest statement

Competing interests: MR, RL, PC, FB, BF, PC, JS, DS, CB and DK are inventors for patent applications related to the therapeutic use of ld-IL2, which belongs to their academic institutions and has been licensed to ILTOO Pharma. MR, VD, JM and DK hold shares in ILTOO Pharma. HPP, VD and JM are employees of ILTOO Pharma. No other potential conflicts of interest relevant to this article were reported.

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