COMPOSITIONS AND METHODS FOR INDUCING IMMUNE TOLERANCE

• US 20130171233A1
• Filed: 07/29/2011
• Published: 07/04/2013
• Est. Priority Date: 07/31/2010
• Status: Active Grant

• Current Assignee: The Scripps Research Institute
• Original Assignee: Matthew Macauley
• Inventors: Paulson, James C., MacAuley, Matthew, Nemazee, David
• Granted Patent: US 9,522,183 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 2039/5154 Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 39/0008 Antigens related to auto-immune diseases; Preparations to induce self-tolerance
• CPC Class Codes: A61K 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• CPC Class Codes: A61K 39/35 Allergens
• CPC Class Codes: A61K 39/385 Haptens or antigens, bound to carriers
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention provides liposomal compositions for inducing immune tolerance. The compounds typically comprise a liposome displaying a specific antigen and also a binding moiety for a sialic acid binding Ig-like lectin (Siglec) expressed on B cells. The invention also provides methods for inducing tolerance to a protein or polypeptide antigen (e.g., a protein antigen) in a subject. The methods involve administering to the subject a pharmaceutical composition that co-presents both the antigen and a glycan ligand for a Siglec expressed on B lymphocytes.

Claims

1. A liposomal composition for inducing immune tolerance to an antigen, comprising a liposome nanoparticle displaying the antigen and a binding moiety for a sialic acid binding Ig-like lectin (Siglec).

2. The liposomal composition of claim 1, wherein the binding moiety comprises a glycan ligand for the Siglec.

3. The liposomal composition of claim 1, wherein the Siglec is a Siglec expressed on B lymphocytes.

4. The liposomal composition of claim 3, wherein the Siglec is CD22 or Siglec-G/10.

5. The liposomal composition of claim 3, wherein the lymphocytes are human lymphocytes.

6. The liposomal composition of claim 5, wherein the glycan ligand is 9-N-biphenylcarboxyl-NeuAcα

2-6Galβ

1-4GlcNAc (6′

-BPCNeuAc), NeuAcα

2-6Galβ

1-4GlcNAc, or NeuAcα

2-6Galβ

1-4(6-sulfo)GlcNAc.

7. The liposomal composition of claim 1, wherein the antigen is a polypeptide.

8. The liposomal composition of claim 7, wherein the antigen is a hapten, a carbohydrate, or a nucleic acid.

9. A pharmaceutical composition comprising the liposomal composition of claim 1.

10. A kit comprising the liposomal composition of claim 1.

11. A method for inducing tolerance to a polypeptide antigen in a subject, comprising administering to the subject a pharmaceutical composition comprising an effective amount of the antigen and a Siglec ligand, thereby inducing immune tolerance to the antigen.

12. The method of claim 11, wherein the antigen is conjugated to the Siglec ligand.

13. The method of claim 11, wherein the antigen and the Siglec ligand are displayed on a liposome.

14. The method of claim 11, wherein the antigen is an autoantigen, an allergen, or an alloantigen.

15. The method of claim 11, wherein the Siglec ligand is a glycan ligand for a Siglec on B lymphocytes.

16. The method of claim 15, wherein the Siglec is CD22 or Siglec-G/10.

17. The method of claim 11, wherein the subject is a human.

18. The method of claim 17, wherein the Siglec ligand is 9-N-biphenylcarboxyl-NeuAcα

2-6Galβ

1-4GlcNAc (6′

-BPCNeuAc), NeuAcα

2-6Galβ

1-4GlcNAc, or NeuAcα

2-6Galβ

1-4(6-sulfo)GlcNAc.

19. A method for suppressing or preventing an undesired immune response to a specific antigen in a subject, comprising administering to the subject a pharmaceutical composition comprising a liposome composition displaying the antigen and a ligand for a sialic acid binding Ig-like lectin (Siglec).

20. The method of claim 19, wherein the antigen is an autoantigen, an allergen, or an alloantigen.

21. The method of claim 19, wherein the Siglec is a Siglec expressed on monocytes or macrophage.

22. The method of claim 19, wherein the Siglec is a Siglec expressed on B lymphocytes.

23. The method of claim 22, wherein the Siglec is CD22 or Siglec-G/10.

24. The method of claim 19, wherein the subject is a human.

25. The method of claim 24, wherein the Siglec ligand is 9-N-biphenylcarboxyl-NeuAcα

2-6Galβ

1-4GlcNAc (6′

-BPCNeuAc), NeuAcα

2-6Galβ

1-4GlcNAc, or NeuAcα

2-6Galβ

1-4(6-sulfo)GlcNAc.