Immunomodulating compositions and methods of use
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.
1. A composition comprising β-1-6-glucan linked to a targeting moiety that targets a neoplastic cell, a pre-neoplastic cell or a component thereof wherein said targeting moiety is an antibody or antigen-binding fragment thereof.
2. The composition of claim 1 , wherein said β-1-6-glucan is isolated or derived from a lichen, a fungus, or a yeast.
3. The composition of claim 1 , wherein said β-1-6-glucan is genetically engineered, or chemically synthesized or acetylated.
4. The composition of claim 1 , wherein the composition is a pharmaceutical composition, a food or food product, a food supplement, or a cosmetic composition.
5. A composition comprising β-1-6-glucan linked to an antibody or antigen-binding fragment thereof.
6. The composition of claim 1 , wherein said targeting moiety is a monoclonal antibody or a human antibody.
7. The composition of claim 1 , wherein said targeting moiety is a humanized antibody.
8. The composition of claim 1 , wherein said targeting moiety is selected from the group consisting of Alemtuzumab, Bevacizumab, Cetuximab, Gemtuzumab, Ibritumomab, Panitumumab, Rituximab, Tositumomab, Trastuzumab, and Palivizumab.
9. The composition of claim 1 , wherein said targeting moiety is a Fab fragment, Fab′ fragment, (Fab′) 2 fragment, Fv fragment, a single chain antibody or a peptide coding for a single complementarity-determining region.
10. A composition comprising β-1-6-glucan linked to a targeting moiety that binds to a tumor antigen wherein said targeting moiety is an antibody or antigen-binding fragment thereof.
11. The composition of claim 1 , wherein said targeting moiety is linked to said β-1-6-glucan via a covalent linkage.
12. The composition of claim 1 , wherein said targeting moiety is linked to said β-1-6-glucan via a non-covalent linkage.
13. The composition of claim 1 , wherein said targeting moiety is linked to said β-1-6-glucan via a linker molecule.
14. The composition of claim 1 , wherein the composition is substantially free of β-1-3-glucan.
15. The composition of claim 1 , wherein at least 90% of the dry weight of glucan contained in the composition is β-1-6-glucan.
16. The composition of claim 1 , wherein said β-1-6-glucan is processed.
17. The composition of claim 1 , wherein said β-1-6-glucan is isolated or derived from Umbilicariaceae.
18. The composition of claim 1 , wherein said targeting moiety is an antibody or antigen-binding fragment thereof that is linked to said β-1-6-glucan via a covalent linkage.
19. The composition of claim 1 , wherein the composition promotes complement-mediated lysis of the neoplastic or pre-neoplastic cell when contacted in vitro with the neoplastic cell or pre-neoplastic cell in the presence of serum.
20. The composition of claim 1 , wherein the composition promotes deposition of C3 or a C3 proteolytic fragment when contacted in vitro with the neoplastic cell or pre-neoplastic cell in the presence of serum.
21. The composition of claim 20 , wherein the C3 proteolytic fragment is selected from the group consisting of C3b, C3d and a combination thereof.
22. The composition of claim 1 , wherein the composition promotes deposition of IgG when contacted in vitro with the neoplastic cell or pre-neoplastic cell in the presence of serum.
23. The composition of claim 1 , wherein the composition promotes recruitment of neutrophils when contacted in vitro with the neoplastic cell or pre-neoplastic cell in the presence of serum and neutrophils.
24. The composition of claim 5 , wherein the composition promotes complement-mediated lysis of a cell that is targeted by the antibody or antigen-binding fragment thereof when contacted in vitro with the cell in the presence of serum.
25. The composition of claim 5 , wherein the composition promotes deposition of C3 or a C3 proteolytic fragment when contacted in vitro, in the presence of serum, with a cell that is targeted by the antibody or antigen-binding fragment thereof.
26. The composition of claim 25 , wherein the C3 proteolytic fragment is selected from the group consisting of C3b, C3d and a combination thereof.
27. The composition of claim 5 , wherein the composition promotes deposition of IgG when contacted in vitro, in the presence of serum, with a cell that is targeted by the antibody or antigen-binding fragment thereof.
28. The composition of claim 5 , wherein the composition promotes recruitment of neutrophils when contacted in vitro, in the presence of serum and neutrophils, with a cell that is targeted by the antibody or antigen-binding fragment thereof.
29. The composition of claim 10 , wherein the composition promotes complement-mediated lysis of a cell that expresses the tumor antigen when contacted in vitro with the cell in the presence of serum.
30. The composition of claim 10 , wherein the composition promotes deposition of C3 or a C3 proteolytic fragment when contacted in vitro, in the presence of serum and neutrophils, with a cell that expresses the tumor antigen.
31. The composition of claim 30 , wherein the C3 proteolytic fragment is selected from the group consisting of C3b, C3d and a combination thereof.
32. The composition of claim 10 , wherein the composition promotes deposition of IgG when contacted in vitro, in the presence of serum, with a cell that expresses the tumor antigen.
33. The composition of claim 10 , wherein the composition promotes recruitment of neutrophils when contacted in vitro, in the presence of serum, with a cell that expresses the tumor antigen.
34. The composition of claim 1 , wherein less than 10% of the total glucan in the composition, by weight, is β-1-3-glucan.
35. The composition of claim 5 , wherein less than 10% of the total glucan in the composition, by weight, is β-1-3-glucan.
36. The composition of claim 5 , wherein the composition is substantially free of β-1-3-glucan.
37. The composition of claim 5 , wherein at least 90% of the dry weight of glucan contained in the composition is β-1-6-glucan.
38. The composition of claim 10 , wherein less than 10% of the total glucan in the composition, by weight, is β-1-3-glucan.
39. The composition of claim 10 , wherein the composition is substantially free of β-1-3-glucan.
40. The composition of claim 10 , wherein at least 90% of the dry weight of glucan contained in the composition is β-1-6-glucan.
41. The composition of claim 5 , wherein said antibody is a monoclonal antibody or a human antibody.
42. The composition of claim 5 , wherein said antibody is a humanized antibody.
43. The composition of claim 5 , wherein said antibody is selected from the group consisting of Alemtuzumab, Bevacizumab, Cetuximab, Gemtuzumab, Ibritumomab, Panitumumab, Rituximab, Tositumomab, Trastuzumab, and Palivizumab.
44. The composition of claim 5 , wherein said antibody or antigen-binding fragment thereof is linked to said β-1-6-glucan via a covalent linkage.
45. The composition of claim 10 , wherein said antibody or antigen-binding fragment thereof is linked to said β-1-6-glucan via a covalent linkage.