BETA-GLUCAN IN COMBINATION WITH ANTI-CANCER AGENTS AFFECTING THE TUMOR MICROENVIRONMENT
The present invention relates to the combination of soluble β-glucan and anti-cancer agents that affect the tumor microenvironment. Soluble β-glucan promotes an immunostimulatory environment, which allows enhanced effectiveness of anti-cancer agents.
1 . A method of treating a subject having cancer, the method comprising administering soluble β(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose and an anti-PD-L1 antibody.
2 . The method according to claim 1 , wherein the cancer is melanoma, renal cell carcinoma, or lung cancer.
3 . The method according to claim 1 , wherein the cancer is breast cancer, pancreatic cancer, colon cancer, and B cell lymphoma.
4 . The method according to claim 1 , wherein the β(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose and the anti-PD-L1 antibody are in a single formulation.
5 . The method according to claim 1 , wherein the β(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose and the anti-PD-L1 antibody are in separate formulations.
6 . The method according to claim 1 , wherein the β(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose is derived from yeast. The method according to claim 6 , wherein the yeast is Saccaromyces cerevisiae.
8 . The method according to claim 1 , wherein the β(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose stimulates the subject's immune system.
9 . The method according to claim 1 , wherein the anti-PD-L1 antibody is a non-complement-activating antibody.
10 . The method according to claim 1 , wherein the anti-PD-L1 antibody is an Fc-engineered IgG 1 antibody.
11 . The method according to claim 1 , wherein the anti-PD-L1 antibody is an IgG 4 antibody.
12 . The method according to claim 1 , wherein the β(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose and the anti-PD-L1 antibody are administered intravenously.
13 . The method according to claim 1 , wherein the method further comprises administration of a tumor targeting antibody.
14 . The method according to claim 1 , wherein the method further comprises beta-glucan antibodies.
15 . The method according to claim 1 , wherein the has high response toward soluble β(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose.
16 . A method of stimulating a subject's immune system against cancer cells, the method comprising administering soluble β(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose and an anti-PD-L1 antibody.
17 . The method according to claim 16 , wherein the immune stimulation comprises activation of M1 macrophages, N1 neutrophils, NK cells, T cells, B cells or dendritic cells.
18 . The method according to claim 16 , wherein the immune stimulation comprises activation of interleukin-12, interferon-γ, tumor-necrosis factor α, or a combination thereof.
19 . A method of removing immune suppression in a tumor microenvironment, the method comprising administering soluble β(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose and an anti-PD-L1 antibody.
20 . The method according to claim 19 , wherein the method comprises suppressin of M2 macrophages, N2 neutrophils, myeloid-derived suppressor cells, or a combination thereof