Immunomodulating compositions and uses therefor
The present invention discloses immunomodulating compositions. More particularly, the present invention discloses compositions comprising an immune-modulating agent and a lectin-interactive agent, which are useful for stimulating and prolonging host immune cell responses. The compositions of the present invention are particularly useful in the treatment and/or prophylaxis of a range of conditions including pathogenic infections, autoimmune diseases, transplant rejection, graft versus host disease, allergies, inflammatory disease, as well as cancers and tumors.
1. An immunomodulating composition comprising:
a galectin interactive agent selected from the group consisting of an antibody that binds to galectin and a soluble, non-metabolizable β-galactoside in a form selected from the group consisting of monosaccharides, disaccharides, larger saccharides, synthetic carbohydrates, glycopeptides, N-acetyllactosamine derivatives, modified polysaccharides, starburst dendrimers and glycopolymers, and
an immune-modulating agent selected from the group consisting of an antigen-binding molecule that is immuno-interactive with a target antigen, and an immune-modulating cell that modulates an immune response to a target antigen.
2. A composition according to claim 1 , wherein the galectin-interactive agent interacts with a galectin selected from the group consisting of galectin-1, galectin-3 and galectin-9.
3. A composition according to claim 1 , wherein the β-galactoside is a synthetic carbohydrate comprising thiodigalactoside.
4. A composition according to claim 1 , wherein the β-galactoside is lactulose.
5. A composition according to claim 1 , wherein the β-galactoside is selected from the group consisting of methyl 2-acetamido-2-deoxy-4-O-(3-[3-carboxypropanamido]-3-deoxy-β-D-galactopyranosyl)-β-D-glucopyranoside, methyl 2-acetamido-2-deoxy-4-O-(3-[{Z}-3-carboxypropenamido]-3-deoxy-β-D-galactopyranosyl)-)β-D-glucopyranoside, methyl 2-acetamido-2-deoxy-4-O-(3-benzamido-3-deoxy-(β-D-galactopyranosyl)-β-D-glucopyranoside, methyl 2-acetamido-2-deoxy-4-O-(3-[2-carboxybenzamido]-3-deoxy-β-D-galactopyranosyl)-β-D-glucopyranoside, methyl 2-acetamido-2-deoxy-4-O-(3-[4-methoxy-2,3,5,6-tetrafluorobenzamido]-3-deoxy-β-D-galactopyranosyl)-β-D-glucopyranoside, methyl 2-acetamido-2-deoxy-4-O-(3-[2-carboxy-3,4,5,6-tetrafluorobenzamido]-3-deoxy-(β-D-galactopyranosyl)-β-D-glucopyranoside, methyl 2-acetamido-2-deoxy-4-O-(3-methane-sulfonamido-3-deoxy-β-D-galactopyranosyl)-β-D-glucopyranoside, methyl 2-acetamido-2-deoxy-4-O-(3-[4-nitrobenzenesulfonamido]-3-deoxy-β-D-galactopyranosyl)-β-D-glucopyranoside, methyl 2-acetamido-2-deoxy-4-O-(3-phenylaminocarbonylamino-3-deoxy-β-D-galactopyranosyl)-(β-D-glucopyranoside, methyl 2-acetamido2-deoxy-4-O-(2-aminoacetamido-3-deoxy-β-D-galactopyranosyl)-β-D-glucopyranoside, and methyl 2-acetamido-2-deoxy-4-O-(3-[{2S}-2-amino-3-carboxy-propanamido]-3-deoxy-β-D-galactopyranosyl)-β-D-glucopyranoside and thiodigalactoside.
6. A composition according to claim 1 , wherein the β-galactoside is selected from the group consisting of methyl 2-acetamido-2-deoxy-4-O-(3-benzamido-3-deoxy-β-D-galactopyranosyl)-β-D-glucopyranoside, methyl 2-acetamido-2-deoxy-4-O-(3-[2-carboxy-benzamido]-3-deoxy-β-D-galactopyranosyl)-β-D-glucopyranoside, methyl 2-acetamido-2-deoxy-4-O-(3-[4-methoxy-2,3,5,6-tetrafluorobenzamido]-3-deoxy-β-D-galactopyranosyl)-β-D-glucopyranoside, and methyl 2-acetamido-2-deoxy-4-O-(3-[2-carboxy-3,4,5,6-tetrafluorobenzamido]-3-deoxy-β-D-galactopyranosyl)-D-glucopyranoside.
7. A composition according to claim 1 , wherein the β-galactoside has a binding affinity for the galectin in the range from about 10 −3 to about 10 −9 M.
8. A composition according to claim 1 , comprising at least two different β-galactosides.
9. A composition according to claim 8 , wherein one of the β-galactosides is soluble so that it can diffuse readily through the body of an animal and wherein the other is a larger β-galactoside that is partially soluble so as to limit its diffusion from the site of delivery to the animal.
10. A composition according to claim 1 , wherein the target antigen is selected from the group consisting of a viral antigen, a bacterial antigen, a fungal antigen, a parasite antigen, an algal antigen, a protozoan antigen, an amoeba antigen and a vertebrate antigen.
11. A composition according to claim 10 , wherein the vertebrate antigen is a mammalian antigen.
12. A composition according to claim 1 , wherein the target antigen is associated with or responsible for a disease or condition.
13. A composition according to claim 12 , wherein the disease or condition is selected from cancers, infectious diseases and diseases characterized by immunodeficiency.
14. A composition according to claim 12 , wherein the disease or condition is a cancer.
15. A composition according to claim 1 , which comprises an antigen-binding molecule that is immuno-interactive with the target antigen, wherein the target antigen is associated with a cancer.
16. A composition according to claim 1 , wherein the immune-modulating cell is an immune effector cell selected from the group consisting of T lymphocytes and B lymphocytes.
17. A composition according to claim 16 , wherein the T lymphocytes are selected from the group consisting of cytolytic T lymphocytes helper T lymphocytes and T regulatory cells.
18. A composition according to claim 1 , wherein the immune modulating agent is an antigen-binding molecule, which binds to or otherwise interacts with the target antigen so as to reduce its level or functional activity.
19. A composition according to claim 1 , further comprising one or more immunoregulatory molecules selected from the group consisting of co-stimulatory molecules, cytokines and co-inhibitory molecules.
20. A composition according to claim 19 , wherein the co-stimulatory molecules are selected from the group consisting of B7-1, B7-2, B7-3, ICAM-1 and ICAM-2.
21. A composition according to claim 19 wherein the cytokines are selected from the group consisting of interferons, granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin-10 and tumor necrosis factor α (TNF-α).
22. A composition according to claim 19 , wherein the co-inhibitory molecules are selected from the group consisting of OX-2 and programmed death-1 ligand (PD-1L).
23. A composition according to claim 19 , wherein the immunoregulatory molecule (s) is/are provided in soluble form.
24. A composition according to claim 19 , wherein the immunoregulatory molecule (s) is/are produced intracellularly from an expression construct or vector.
25. A composition according to claim 1 , further comprising an adjuvant.
26. A composition according to claim 1 , further comprising a pharmaceutically acceptable carrier.
27. An immunomodulating composition comprising:
a galectin interactive agent selected from the group consisting of an antibody that binds to galectin and a soluble, non-metabolizable β-galactoside in a form selected from the group consisting of monosaccharides, disaccharides, larger saccharides, synthetic carbohydrates, glycopeptides, N-acetyllactosamine derivatives, modified polysaccharides, starburst dendrimers and glycopolymers, and
an antigen-binding molecule that is immuno-interactive with a target antigen.
28. An immunomodulating composition comprising:
a galectin interactive agent selected from the group consisting of an antibody that binds to galectin and a soluble, non-metabolizable β-galactoside in a form selected from the group consisting of monosaccharides, disaccharides, larger saccharides, synthetic carbohydrates, glycopeptides, N-acetyllactosamine derivatives, modified polysaccharides, starburst dendrimers and glycopolymers, and
an immune-modulating cell that modulates an immune response to a target antigen.
29. A method for modulating an immune response in a subject, comprising administering to the subject the composition according to claim 1 .
30. A method according to claim 29 , wherein the galectin interactive agent and the immune-modulating agent are administered sequentially, separately or simultaneously.
31. A method according to claim 29 , wherein the method for modulating an immune response is used for the treatment of a disease or condition associated with the presence or aberrant expression of the target antigen in the subject.
32. A method according to claim 31 , wherein the disease or condition is selected from the group consisting of a pathogenic infection, a disease characterized by immunodeficiency and a cancer or tumor.
33. A method according to claim 31 , wherein the disease or condition is an inflammatory disease.
34. A method according to claim 31 , wherein the disease or condition is a cancer or tumor.
35. A method according to claim 31 , wherein the disease or condition is selected from the group consisting of transplant rejection, graft versus host disease, allergies, parasitic diseases and autoimmune diseases.