IMMUNOMODULATING COMPOSITIONS AND METHODS OF USE

• US 20110045049A1
• Filed: 11/06/2007
• Published: 02/24/2011
• Est. Priority Date: 11/06/2006
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.), Trustees of Boston University, Whitehead Institute
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Kohane, Danial S., Fuller, Jason E., Rubin-Bejerano, Ifat, Langer, Robert S., Abeijon, Claudia, Fink, Gerald R.
• Granted Patent: US 8,580,253 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/716 Glucans
• CPC Class Codes: A61K 36/09 Lichens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 8/73 Polysaccharides
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin

Abstract

This invention is directed to β-1-6-glucans, compositions and devices comprising the same, and methods of use thereof in modulating immune responses. The β-1-6-glucans of certain embodiments of the invention are enriched for O-acetylated groups and/or conjugated to a solid support or linked to a targeting moiety.

Claims

1. A composition comprising β

-1-6-glucan optionally enriched for O-acetylated groups.

2. The composition of claim 1, wherein said glucan contains at least 25% by weight O-acetylated glucan.

3. The composition of claim 1, wherein said glucan is isolated or derived from a lichen, a fungus, a yeast or Umbilicariaceae.

5. The composition of claim 1, wherein said glucan is genetically engineered, or chemically synthesized or acetylated.

6. The composition of claim 1, further comprising an adjuvant, an antigen, an immuno-modulatory compound, a targeting moiety or a combination thereof.

7. The composition of claim 1, wherein said glucan is conjugated to a particle or solid support.

8. A method of modulating an immune response in a subject, said method comprising administering to said subject the composition of claim 1.

12. The method of claim 8, wherein said composition further comprises an adjuvant, an antigen, an immuno-modulatory compound, a targeting moiety or a combination thereof.

14. The method of claim 8, wherein modulating said immune response comprises stimulating said immune response.

15. The method of claim 8, wherein said immune response is an antigen-specific response.

16. The method of claim 8, wherein said composition further comprises a chemotherapeutic compound or an immunostimulatory compound.

17. The method of claim 8, wherein said immune response is complement-dependent.

18. The method of claim 8, wherein said immune response is directed against an infectious agent, a cancer, a preneoplastic lesion or a combination thereof.

19. The method of claim 18, wherein said infectious agent causes sepsis.

20. The method of claim 18, wherein said infectious agent is a parasite, helminth, virus or bacteria.

21. The method of claim 8, wherein modulating said immune response comprises downmodulating or abrogating said immune response.

22. The method of claim 21, wherein said composition further comprises an immunosuppressant.

23. The method of claim 21, wherein said immune response is directed against an autoantigen, an allergen, transplanted tissue or cells.

31. The composition of claim 7, further comprising an adjuvant, an antigen, an immuno-modulatory compound, a targeting moiety or a combination thereof.

32. The composition of claim 7, wherein said particle is a microsphere or nanoparticle.

33. The composition of claim 32, wherein said microsphere has a diameter of about 0.1-15 microns.

52. A method of treating, delaying progression of, prolonging remission of, or reducing the incidence or severity of cancer or an infection in a subject, said method comprising administering to said subject the composition of claim 1.

58. The method of claim 52, further comprising administering an adjuvant, an antigen, a peptide, an immuno-stimulatory compound, a chemotherapeutic compound or a combination thereof.

59. The method of claim 58, wherein said antigen is a tumor-associated antigen or an antigen derived from the source of infection.

60. The method of claim 58, wherein said peptide is derived from a tumor-associated antigen or from a source of infection.

61. The method of claim 58, wherein said immuno-stimulatory compound is a cytokine.

63. The method of claim 52, wherein said subject has a hyperplastic or preneoplastic lesion.

64. The method of claim 52, wherein said glucan is linked to a targeting moiety.

65. The method of claim 64, wherein said targeting moiety specifically interacts with a tumor-associated antigen.

75. The method of claim 58, wherein said chemotherapeutic compound is an antibiotic or antiviral compound.

80. A method of stimulating or enhancing heat shock protein expression in a cell, the method comprising contacting said cell with the composition of claim 1.

81. The method of claim 80, wherein said glucan is attached to a particle.

86. The method of claim 80, wherein said cell is an antigen-presenting cell.

87. The method of claim 86, wherein said cell is a neutrophil.

88. The method of claim 86, wherein said cell is infected.

99. The composition of claim 7, wherein the particle comprises at least 50% β

-1-6-glucan by weight.

100. The composition of claim 7, wherein the particle comprises glucan, and wherein at least 50% of the glucan is β

-1-6-glucan

101. The composition of claim 7, wherein the β

-1-6-glucan is homogeneously distributed in the particle.

102. The composition of claim 7, wherein the particle has a size appropriate for phagocytosis by neutrophils, monocytes, macrophages, or dendritic cells.

107. The composition of claim 1, wherein the composition is a pharmaceutical composition, a food or food product, a food supplement, or a cosmetic composition.

108. The composition of claim 107, wherein the composition comprises β

-1-6-glucan that has been processed to increase its ability to modulate the immune response relative to unprocessed β

-1-6-glucan.

109. The composition of claim 107, wherein at least 50% of the glucan contained in the composition is β

-1-6-glucan.

112. A micelle comprising the composition of claim 1.

113. A composition comprising the composition of claim 1 and a biodegradable polymer, wherein said biodegradable polymer degrades to form biologically active salicylate or alpha-hydroxy acid moieties.

114. A particle or medical device comprising the composition of claim 113.

116. A medical device wherein at least a portion of a surface of the implant or device comprises or is coated with the composition of claim 1.

118. The medical device of claim 116, wherein the device is selected from the group consisting of:

catheter, stent, valve, pacemaker, central line, pessary, tube, shunt, feeding tube, drain, and orthopedic hardware devices.

120. The medical device of claim 116, wherein the polymer is biodegradable.

122. A coated material comprising:

(a) a substrate; and

(b) composition of claim 1 physically associated with at least a portion of a surface of said substrate, wherein said composition is optionally in the form of a gel or film.

123. The coated material of claim 122, wherein the composition comprises a polymer.

124. The coated material of claim 122, wherein the composition comprises a biodegradable polymer.

125. The coated material of claim 122, wherein the substrate is composed at least in part of metal, ceramic, or polymer.

127. The composition of claim 6 wherein the β

-1-6-glucan is physically associated with a targeting moiety.

136. The composition of claim 6, wherein said targeting moiety is an antibody or antibody fragment.

151. The method of claim 12, wherein the targeting moiety is an antibody or antibody fragment.

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