Compositions and methods for inducing immune tolerance

• US 9,522,183 B2
• Filed: 07/29/2011
• Issued: 12/20/2016
• Est. Priority Date: 07/31/2010
• Status: Active Grant

• Current Assignee: The Scripps Research Institute
• Original Assignee: The Scripps Research Institute
• Inventors: Paulson, James C., Macauley, Matthew, Nemazee, David
• Primary Examiner(s): Kelly, Robert M
• Application Number:
  US13/261,580
• Publication Number:
  US 20130171233A1
• Time in Patent Office: 1,971 Days
• US Class Current: 1/1
• 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 method for reducing antigen-specific antibodies to a polypeptide antigen in a subject, comprising administering to the subject a pharmaceutical composition comprising a liposome;

a CD22, Siglec G, or Siglec-10 glycan ligand; and

an effective amount of a T cell-dependent MHC class II, B cell-specific polypeptide antigen that is linked to a lipid and co-displayed on the liposome with the CD22, Siglec G, or Siglec-10 glycan ligand;

to thereby reduce production of antibodies to the antigen by B cells in the subject.

2. The method of claim 1, wherein the antigen is an autoantigenan or an alloantigen.

3. The method of claim 1, wherein the subject is a human.

4. The method of claim 3, 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.

5. The method of claim 1, wherein the polypeptide antigen is a self-antigen, an autoantigen, an alloantigen, a food antigen, or a tissue specific antigen.

6. The method of claim 1, wherein the polypeptide antigen is a foreign antigen.

7. The method of claim 1, wherein the administering is parenteral administration.