Fungal immunostimulatory compositions

• US 20070231339A1
• Filed: 10/13/2006
• Published: 10/04/2007
• Est. Priority Date: 10/14/2005
• Status: Active Grant

• Current Assignee: Academia Sinica (Government of The Republic of China)
• Original Assignee: Academia Sinica (Government of The Republic of China)
• Inventors: Wong, Chi-Huey, Yu, Alice, Yu, John, Yang, Wen-Bin, Lin, Kuo-I
• Granted Patent: US 8,906,380 B2
• Time in Patent Office: Days
• US Class Current: 424/184.100
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 36/074 Ganoderma
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/4614 Monocytes; Macrophages
• CPC Class Codes: A61K 39/4615 Dendritic cells
• CPC Class Codes: A61K 39/4622 Antigen presenting cells
• CPC Class Codes: A61K 39/4641 Fungal antigens, e.g. Trichophyton, Aspergillus or Candida
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: C12N 2500/74 from fungi, e.g. yeasts
• CPC Class Codes: C12N 5/0639 Dendritic cells, e.g. Langherhans cells in the epidermis

Abstract

Methods are disclosed which are useful in increasing maturation of dendritic cells from CD14⁺ mononuclear cells, by contact with a composition comprising a fucose-containing glycoprotein fraction from Ganoderma lucidum. The extract can also be used for increasing production of a cytokine or a chemokine in a dendritic cell or CD19⁺ B cell. In addition, a fucose-containing glycoprotein fraction from Ganoderma lucidum can be administered to a subject identified as needing increased immunoglobulin, cytokine, or chemokine production.

Claims

1. A method for increasing maturation of a dendritic cell, the method comprising contacting a CD14⁺ mononuclear cell with a composition comprising a fucose-containing glycoprotein fraction from Ganoderma lucidum.

2. The method of claim 1, further comprising subsequent introduction of the dendritic cell into a subject identified as in need thereof.

3. A method for increasing immunoglobulin production in a subject identified as in need thereof, the method comprising administering to the subject an effective amount of a composition comprising a fucose-containing glycoprotein fraction from Ganoderma lucidum.

4. The method of claim 3, wherein the immunoglobulin is immunoglobulin G or immunoglobulin M.

5. The method of claim 3, wherein the subject is identified as suffering from hypogammaglobulinemia, common variable immunodeficiency, immunodeficiency associated with cancer, or immunosuppression prior to the administration.

6. A method of increasing an immune response to an antigen in a subject identified as in need thereof, the method comprising contacting a cell population containing CD14⁺ mononuclear cells with the antigen and with a composition comprising a fucose-containing glycoprotein fraction from Ganoderma lucidum.

7. The method of claim 6, wherein the contacting is performed by administration of the antigen and the composition to the subject.

8. The method of claim 7, wherein routes of the administration of the antigen and the composition are different.

9. The method of claim 6, wherein the contacting is performed ex vivo, and the population of contacted cells is subsequently administered to the subject.

10. The method of claim 9, wherein the population is enriched for CD14⁺ mononuclear cells.

11. The method of claim 6, wherein the antigen is derived from a pathogen.

12. The method of claim 11, wherein the pathogen causes diphtheria, tetanus, pertussis, polio, Haemophilus Influenzae type b, hepatitis, pneumonia, meningitis, otitis media, influenza, avian flu, chicken pox, rubeola, or rubella.

13. The method of claim 6, wherein the antigen is expressed in a cancer cell.

14. A method of increasing production of a cytokine or chemokine by a dendritic cell, the method comprising contacting the dendritic cell with a composition comprising a fucose-containing glycoprotein fraction from Ganoderma lucidum, wherein the cytokine or chemokine is IL-1α

, IL-1β

, IL-3, IL-6, IL-7, IL-8, IL-10, IL 12p40, IL 12p70, IFN-K, TNF-α

, Eotaxin, IP-10, MCP-1, MIP-1α

, or RANTES.

15. The method of claim 14, wherein the cytokine or chemokine is IL-1α

, IL-3, IL-7, IL-8, IL-10, Eotaxin, IP-10, MCP-1, MIP-1α

, or RANTES.

16. The method of claim 14, wherein the dendritic cell is derived from an enriched CD14⁺ mononuclear cell population.

17. The method of claim 16, wherein the contacted dendritic cell is transferred to a subject identified as in need of increased levels of a cytokine or chemokine produced by a dendritic cell.

18. A method of increasing levels of a cytokine or chemokine produced by a human CD19⁺ B cell, comprising contacting the cell with a composition comprising a fucose-containing glycoprotein fraction from Ganoderma lucidum, wherein the cytokine or chemokine is IL-6, IL-8, or MIP-1α

.

19. The method of claim 18, wherein the CD19⁺ B cell is derived from an enriched CD19⁺ B cell population.

20. The method of claim 19, wherein the contacted CD19⁺ B cell is transferred to a subject identified as in need of increased levels of a cytokine or chemokine produced by a human CD19⁺ B cell.

21. The method of claim 20, wherein the subject is also identified as in need of an increased immunoglobulin level produced by a CD19⁺ B cell.

22. A method of increasing production of a cytokine or chemokine in a subject identified as in need thereof, the method comprising administering a composition comprising a fucose-containing glycoprotein fraction from Ganoderma lucidum to the subject, wherein the cytokine or chemokine is IL 1α

, IL-1β

, IL-3, IL-6, IL-7, IL-8, IL-10, IL 12p40, IL-12p70, IFN-K, TNF-α

, Eotaxin, IP-10, MCP-1, MIP-1α

, or RANTES.

23. The method of claim 22, wherein the cytokine or chemokine is IL-1α

, IL-3, IL-7, IL-8, IL-10, Eotaxin, IP-10, MCP-1, MIP-1α

, or RANTES.

24. An immunostimulatory composition comprising a fucose-containing glycoprotein fraction from Ganoderma lucidum and at least one antigen.

25. The composition according to claim 24, further comprising one or more components selected from the group consisting of:

surfactants, absorption promoters, water absorbing polymers, substances which inhibit enzymatic degradation, alcohols, organic solvents, oils, pH-controlling agents, solubilizers, stabilizers, HLB-controlling agents, viscosity controlling agents, preservatives, osmotic pressure controlling agents, propellants, air displacement, water, and mixtures thereof.

26. The composition according to claim 24, wherein the antigen is selected from the group consisting of a tumor antigen, tetanus toxoid, hemagglutinin molecules from influenza virus, cancer antigen, diphtheria toxoid, HIV gp120, IgA protease, insulin peptide B, Spongospora subterranea antigen, vibriose antigens, Salmonella antigens, pneumococcus antigens, respiratory syncytial virus antigens, Haemophilus influenza outer membrane proteins, Helicobacter pylori urease, Neisseria meningitidis pilins and N. gonorrhoeae pilins.

27. An immunostimulatory nasal formulation composition suitable for delivery to the nasal mucosa, the composition comprising between about 0.01 to about 70% v/v of a fucose-containing glycoprotein fraction from Ganoderma lucidum and further comprising at least one antigen.

28. An orally administrable immunostimulatory pharmaceutical composition useful in producing a protective immune response in a host to an antigen specific for a pathogen comprising an admixture of an effective amount of the antigen and an adjuvant comprising a fucose-containing glycoprotein fraction from Ganoderma lucidum in an orally acceptable pharmaceutical composition.

29. A method of augmenting the ability of an antigen presenting cell (APC) to present a tumor antigen to the immune system, the method comprising:

(a) contacting the antigen presenting cell with a composition comprising a fucose-containing glycoprotein fraction from Ganoderma lucidum; and

(b) contacting the antigen presenting cell with at least one tumor antigen.

30. The method of claim 29 wherein the antigen presenting cell is a dendritic cell or a macrophage.

31. The method of claim 29 wherein steps (a) and (b) are performed ex vivo and further comprising:

(c) introducing the antigen presenting cell into a subject carrying a tumor that displays said tumor antigen.