LIPOSOME TARGETING COMPOUNDS AND RELATED USES

• US 20130164364A1
• Filed: 07/29/2011
• Published: 06/27/2013
• 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., Chen, Weihsu Claire, Kawasaki, Norihito, Nycholat, Corwin
• Granted Patent: US 9,326,939 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 49/0084 liposome, i.e. bilayered vesicular structure
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• 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 liposome targeting compounds for targeting cells expressing sialic acid binding Ig-like lectin (Siglec). The liposome compounds typically comprise a binding moiety that is a glycan ligand of the Siglec on the target cell. The liposome compounds also incorporate or encapsulate a biological agent (e.g., an antigen or a therapeutic agent) that can be delivered to the target cell to modulate or kill the target cell. The invention also provides methods of using the liposome targeting compounds for targeted delivery of antigen and for modulating immune cells or immune responses.

Claims

1. A liposome targeting compound comprising (1) a liposome nanoparticle displaying a binding moiety for a sialic acid binding Ig-like lectin (Siglec) on a target cell, and (2) an antigen or an immune modifying agent incorporated by the liposome.

2. The targeting compound of claim 1, wherein the biding moiety is a glycan ligand for the Siglec.

3. The targeting compound of claim 2, wherein the glycan ligand is 9-N-biphenylcarboxyl-NeuAcα

2-3Galβ

1-4GlcNAc (3′

-^BPCNeuAc), 9-N-biphenylacetyl-NeuGcα

2-6Galβ

1-4GlcNAc (^BPANeuGc), or 9-N-biphenylcarboxyl-NeuAcα

2-6Galβ

1-4GlcNAc (6′

-^BPCNeuAc).

4. The targeting compound of claim 1, wherein the target cell is an antigen presenting cell.

5. The targeting compound of claim 4, wherein the antigen presenting cell is a B cell, a macrophage, or a dendritic cell.

6. The targeting compound of claim 1, wherein the Siglec is CD22 or sialoadhesin.

7. The targeting compound of claim 1, wherein the antigen is a protein, a peptide, a lipid-linked antigen, or a polysaccharide.

8. The targeting compound of claim 7, wherein the immune modifying agent is a cytokine or a polynucleotide.

9. A method for targeting an antigen to an antigen presenting cell, comprising (a) preparing a liposome targeting compound displaying a glycan ligand for the Siglec on an antigen presenting cell, wherein the liposome incorporates the antigen;

and (b) contacting the liposome targeting compound with the antigen presenting cell.

10. The method of claim 9, wherein the antigen presenting cell is a B cell, a macrophage, or a dendritic cell.

11. The method of claim 9, wherein the Siglec is CD22 or sialoadhesin.

12. The method of claim 9, wherein the glycan ligand is 9-N-biphenylcarboxyl-NeuAcα

2-3Galβ

1-4GlcNAc (3′

-^BPCNeuAc), 9-N-biphenylacetyl-NeuGcα

2-6Galβ

1-4GlcNAc (^BPANeuGc), or 9-N-biphenylcarboxyl-NeuAcα

2-6Galβ

1-4GlcNAc (6′

-^BPCNeuAc).

13. The method of claim 9, wherein the liposome targeting compound is contacted with the antigen presenting cell in vitro.

14. The method of claim 9, wherein the liposome targeting compound is administered to a subject and contacted with the antigen presenting cell inside the body of the subject.

15. A method for modulating an immune response to an antigen, comprising (a) preparing a liposome targeting compound displaying a glycan ligand for the Siglec on an antigen presenting cell, wherein the liposome incorporates the antigen;

and (b) contacting the liposome targeting compound with the antigen presenting cell;

thereby modulating an immune response to the antigen.

16. The method of claim 15, wherein the antigen presenting cell is a B cell, a macrophage, or a dendritic cell.

17. The method of claim 15, wherein the antigen is a protein antigen, and wherein the modulated immune response is activation of CD4⁺ and CD8⁺ T cells.

18. The method of claim 15, wherein the antigen is an activator of natural killer T (NKT) cells, and wherein the modulated immune response is activation of NKT cells.

19. The method of claim 15, wherein the liposome targeting compound is contacted with the antigen presenting cell in vitro.

20. The method of claim 15, wherein the liposome targeting compound is administered to a subject and contacted with the antigen presenting cell inside the body of the subject.