US-12617837-B2 - Composition for use in treatment of allergic diseases

Abstract

The present invention provides a composition and method for treating an allergic disease. The composition comprises a ligand for asialoglycoprotein receptor 1 (Asgr1). The allergic disease may be atopic dermatitis, allergic rhinitis, urticaria, allergic asthma, allergic conjunctivitis, allergic gastrointestinal inflammation, or anaphylactic shock. The allergic disease may be caused by house dust mites. The present invention also provides a method for determining if a test compound activates human Asgr1.

Inventors

• Akira Shibuya
• Kazumasa KANEMARU

Assignees

• UNIVERSITY OF TSUKUBA

Dates

Publication Date

20260505

Application Date

20200228

Priority Date

20190301

Claims (12)

1. 1 . A method of treating an allergic disease, comprising: administering a composition comprising a ligand for asialoglycoprotein receptor 1 (Asgr1) to a subject in need thereof.
2. 2 . The method of claim 1 , wherein the allergic disease is at least one selected from the group consisting of atopic dermatitis, allergic rhinitis, urticaria, allergic asthma, allergic conjunctivitis, allergic gastrointestinal inflammation, and anaphylactic shock.
3. 3 . The method of claim 1 , wherein the allergic disease is caused by a house dust mite.
4. 4 . The method of claim 1 , wherein the subject is a human.
5. 5 . The method of claim 1 , wherein the ligand comprises a polymeric scaffold presenting at least one glycan selected from the group consisting of a T antigen, a Tn antigen, and LeA, provided that the ligand is neither mucin nor a mucin-like protein and does not contain LeX.
6. 6 . The method of claim 5 , wherein the polymeric scaffold comprises at least one polymer selected from the group consisting of polylactic acid, polyacrylamide, polyvinyl, polyvinyl alcohol, polymethyl methacrylate, polyacrylonitrile, polystyrene, polypropylene, polyethylene terephthalate, nylon, collagen, hydroxyethyl methacrylate, chitosan, chitin, polyethylene oxide, polyethylene glycol, polyamino acid, polylactide, polyglycolide, polycaprolactone, and a copolymer thereof.
7. 7 . The method of claim 1 , wherein the composition is in a form of a gel, an emulsion, a cream, a liquid, a paste, a lotion, or a liposome cream.
8. 8 . The method of claim 1 , wherein the composition further comprises an effective amount of a pharmaceutically acceptable additive.
9. 9 . The method of claim 8 , wherein the pharmaceutically acceptable additive is at least one selected from the group consisting of a solvent, a base, a diluent, a volume filler, and an auxiliary.
10. 10 . The method of claim 8 , wherein the pharmaceutically acceptable additive is at least one selected from the group consisting of a dissolution aid, a solubilizer, a buffer, an isotonizing agent, an emulsifier, a suspending agent, a dispersant, a thickener, a gelling agent, a curing agent, an absorbent, an adhesive, an elastic agent, a plasticizer, a sustained release agent, and a propellant.
11. 11 . The method of claim 1 , wherein the ligand positively regulates a downstream signal of asialoglycoprotein receptor 1 (Asgr1) by binding to the receptor.
12. 12 . The method of claim 1 , wherein the ligand comprises at least one glycan selected from the group consisting of a T antigen, a Tn antigen and LeA, and positively regulates a downstream signal of asialoglycoprotein receptor 1 (Asgr1) by binding thereto, provided that the ligand is neither mucin nor a mucin-like protein and does not contain LeX.

Description

TECHNICAL FIELD The present invention relates to a composition for use in treatment of an allergic disease. BACKGROUND ART House dust mites (HDMs) are major allergens of allergic diseases such as atopic dermatitis and asthma (Non Patent Literatures 1 and 2). NC/Nga mouse is a mouse strain which is sensitive to HDM and develop more severe dermatitis due to HDM as compared with other strains (Non Patent Literature 3). However, a mechanism of pathogenesis of dermatitis is largely unknown. CITATION LIST Patent Literature Non Patent Literature 1: Bieber, T. N. Engl. J. Med., 358: 1483-1494, 2008Non Patent Literature 2: Jacquet, A., Trends Mol. Med., 17: 604-611, 2011Non Patent Literature 3: Yamamoto, M. et al., Arch. Dermatol. Res., 301: 739-746, 2009 SUMMARY OF INVENTION The present invention provides a composition for use in treatment of an allergic disease. The present inventors discovered that Clec10a is involved in the development and exacerbation of dermatitis due to house dust mites in mice. The present inventors also discovered that, in humans a structural functional counterpart of Clec10a is Asgr1, and also, in humans, Asgr1 is involved in the development and exacerbation of dermatitis by house dust mites. The present inventors further discovered that house dust mites contain a substance which binds to mouse Clec10a and human Asgr1 and which suppresses the development of allergies (e.g., Clec10a ligand or Asgr1 ligand). The present inventors further discovered that the Clec10a ligand includes an O-linked glycan, in particular, a T antigen (Galβ(1-3)GalNAc) or a Tn antigen (αGalNAc), and that ASGR1 binds to both of them. The present invention is based on these findings. That is, the present invention provides, for example, the following inventions. (1) A composition for use in treatment of an allergic disease, the composition including a ligand for asialoglycoprotein receptor 1 (Asgr1).(2) The composition according to (1), wherein the allergic disease is one or more selected from the group consisting of atopic dermatitis, allergic rhinitis, urticaria, allergic asthma, allergic conjunctivitis, allergic gastrointestinal inflammation and anaphylactic shock.(3) The composition according to (1) or (2), wherein the allergic disease is caused by a house dust mite.(4) The composition according to any one of (1) to (3), wherein the ligand includes either or both of a T antigen and a Tn antigen.(5) The composition according to any one of (1) to (3), wherein the ligand is a glycan selected from the group consisting of a T antigen and a Tn antigen.(6) The composition according to any one of (1) to (4), wherein the ligand is a mucin-like protein or mucin.(7) The composition according to any one of (1) to (6), wherein the ligand is a ligand for human asialoglycoprotein receptor 1. The present invention also provides the following inventions. (1A) A composition for use in treatment of an allergic disease, including a ligand for asialoglycoprotein receptor 1 (Asgr1).(2A) The composition according to (1A), wherein the allergic disease is one or more selected from the group consisting of atopic dermatitis, allergic rhinitis, urticaria, allergic asthma, allergic conjunctivitis, allergic gastrointestinal inflammation and anaphylactic shock.(3A) The composition according to (1A) or (2A), wherein the allergic disease is caused by a house dust mite.(4A) The composition according to any one of (1A) to (3A), wherein the ligand includes at least one glycan selected from the group consisting of a T antigen, a Tn antigen, LeA, and Lex.(5A) The composition according to any of (1A) to (3A), wherein the ligand includes a polymeric scaffold presenting at least one glycan selected from the group consisting of a T antigen, a Tn antigen, LeA, and Lex.(6A) The composition according to any one of (1A) to (4A), wherein the ligand is a mucin-like protein or mucin.(7A) The composition according to any one of (1A) to (6A), wherein the ligand is a ligand for human asialoglycoprotein receptor 1.(8A) An animal cell expressing a fusion protein including an extracellular region and a transmembrane region of human asialoglycoprotein receptor 1, and an intracellular region of CD3ζ, the animal cell having a gene encoding a reporter operably linked to a promoter activated by a CD3ζ signal.(9A) A method of testing that a test compound is a compound that activates human asialoglycoprotein receptor 1, the method including:contacting the cell described in (8A) with a test compound; and determining that the test compound is a compound that binds to human asialoglycoprotein receptor 1 when a reporter expression level is enhanced. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 shows that a nonsense mutation in Clec10a in NC/Nga mice causes HDM-induced dermatitis. Panel a shows Clec10a genes and DNA sequences of nonsense mutation sites (c.706) in C57BL/6J Clec10a (NM_010796), NC/Nga-Clec10ac.706T/T (c.706T/T), and NC/Nga-Clec10ac.706 T/C (c.706T/C) mice. The total length