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1. WO2020064702 - USE OF ANTAGONISTS OF TH17 CYTOKINES FOR THE TREATMENT OF BRONCHIAL REMODELING IN PATIENTS SUFFERING FROM ALLERGIC ASTHMA

Publication Number WO/2020/064702
Publication Date 02.04.2020
International Application No. PCT/EP2019/075654
International Filing Date 24.09.2019
IPC
C07K 16/24 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
24against cytokines, lymphokines or interferons
C07K 16/28 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
28against receptors, cell surface antigens or cell surface determinants
A61P 11/06 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
11Drugs for disorders of the respiratory system
06Antiasthmatics
A61K 39/395 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
G01N 33/50 2006.01
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48Biological material, e.g. blood, urine; Haemocytometers
50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
G01N 33/569 2006.01
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48Biological material, e.g. blood, urine; Haemocytometers
50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
53Immunoassay; Biospecific binding assay; Materials therefor
569for microorganisms, e.g. protozoa, bacteria, viruses
CPC
A61P 11/06
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
11Drugs for disorders of the respiratory system
06Antiasthmatics
C07K 16/244
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
24against cytokines, lymphokines or interferons
244Interleukins [IL]
C07K 16/2866
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
28against receptors, cell surface antigens or cell surface determinants
2866against receptors for cytokines, lymphokines, interferons
C07K 2317/76
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2317Immunoglobulins specific features
70characterized by effect upon binding to a cell or to an antigen
76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
G01N 2333/54
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
2333Assays involving biological materials from specific organisms or of a specific nature
435from animals; from humans
52Assays involving cytokines
54Interleukins [IL]
G01N 2800/122
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
2800Detection or diagnosis of diseases
12Pulmonary diseases
122Chronic or obstructive airway disorders, e.g. asthma COPD
Applicants
  • INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) [FR]/[FR]
  • UNIVERSITÉ DE LILLE [FR]/[FR]
  • CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) [FR]/[FR]
  • INSTITUT PASTEUR DE LILLE [FR]/[FR]
  • CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE LILLE [FR]/[FR]
Inventors
  • TSICOPOULOS, Anne
  • AIT YAHIA SENDID, Saliha
  • NANOU, Julie
  • BOUTE, Mélodie
  • VORNG, Han
  • CHENIVESSE, Cécile
Agents
  • INSERM TRANSFERT
Priority Data
18306243.925.09.2018EP
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) USE OF ANTAGONISTS OF TH17 CYTOKINES FOR THE TREATMENT OF BRONCHIAL REMODELING IN PATIENTS SUFFERING FROM ALLERGIC ASTHMA
(FR) UTILISATION D'ANTAGONISTES DE CYTOKINES TH17 POUR LE TRAITEMENT DU REMODELAGE BRONCHIQUE CHEZ DES PATIENTS SOUFFRANT D'ASTHME ALLERGIQUE
Abstract
(EN)
Bronchial remodelling is a prominent feature of severe asthma and a potential therapeutic target. Some data indicate that Th17 cytokines in particular IL-22 may be involved in remodelling processes in vitro, and in skin remodelling in vivo. The aim of the inventors was to evaluate if Th17 cytokines are involved in bronchial remodelling in a severe model of allergic asthma, and if this was amplified by co-sensitization with NOD2 agonist, MDP, a ligand favouring Th17 polarization. Dog allergen challenge led to a predominant neutrophilic infiltration in Broncho-alveolar lavage (BAL), increased dog-specific IgE production, airways hyperresponsiveness, and increased Thl7 cytokine production. Increased bronchial remodeling was observed in dog allergen challenged mice compared to control. IL-22 deficiency decreased airway hyperresponsiveness, bronchial mucus production as well as peribronchial collagen deposition, in the allergen-challenged group. Th17 cytokines in particular IL-22 participate in the bronchial remodeling in a chronic model of neutrophilic asthma, and may represent a therapeutic target in severe asthma.
(FR)
Le remodelage bronchique est une caractéristique importante de l'asthme sévère et une cible thérapeutique potentielle. Certaines données indiquent que les cytokines Th17, en particulier IL-22 peuvent être impliquées dans des processus de remodelage in vitro, et dans le remodelage de la peau in vivo. L'objectif de la présente invention est d'évaluer si des cytokines Th17 sont impliquées dans le remodelage bronchique dans un modèle d'asthme allergique sévère, et si cela a été amplifié par co-sensibilisation avec un agoniste NOD2, un MDP, un ligand favorisant la polarisation de Th17. Le test d'allergène de chien conduit à une infiltration neutrophile prédominante dans un lavage broncho-alvéolaire (BAL), une production d'IgE spécifique du chien accrue, une hyperréactivité des voies respiratoires, et une production accrue de cytokines Thl7. Une augmentation du remodelage bronchique a été observée chez des souris déficientes en allergènes de chien par rapport au témoin. La carence en IL-22 diminue l'hyperréactivité des voies respiratoires, la production du mucus bronchique ainsi que le dépôt de collagène péribronchique, dans le groupe ayant subi une provocation par allergène. Les cytokines Th17, en particulier IL-22 participent au remodelage bronchique dans un modèle chronique de l'asthme neutrophile, et peuvent représenter une cible thérapeutique dans l'asthme sévère.
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