NK CELL-BASED THERAPY
Disclosed herein are methods of cancer treatment comprising administration of a natural killer (NK) cell or cell line in combination with an IL-6 antagonist, such as an antibody to IL-6 or its receptor, especially for treatment of cancer expressing IL-6 receptors and in which checkpoint inhibitory receptors, such as PDL-1 and/or PDL-2 are expressed/upregulated during disease.
1 . A method of treating cancer comprising administering to a patient an effective amount of a composition comprising an NK cell and an IL-6 antagonist.
2 . The method of claim 1 , wherein the cancer expresses IL-6 receptors.
3 . The method of claim 1 , wherein the cancer expresses PDL-1, PDL-2, or a combination thereof.
4 . The method of claim 1 , comprising administering to the patient an effective amount of an NK cell pre-bound with the IL-6 antagonist.
5 . The method of claim 1 , wherein the IL-6 antagonist is an antibody that binds one of IL-6, IL-6R and gp130.
6 . The method of claim 1 , wherein the antagonist is an IL-6 antibody selected from the group consisting of siltuximab, olokizumab (CDP6038), elsilimomab, BMS-945429 (ALD518), MH-166, and sirukumab (CNTO 136).
7 . The method of claim 1 , wherein the cancer is a blood cancer selected from the group consisting of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CIVIL), hairy cell leukemia, T-cell prolymphocytic leukemia, large granular lymphocytic leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, including T-cell lymphomas and B-cell lymphomas, asymptomatic myeloma, smoldering multiple myeloma (SMM), multiple myeloma (MM), and light chain myeloma.
8 . The method of claim 1 , wherein the NK cell is KHYG-1.
9 . A method of treating cancer selected from (i) IL-6 receptor expressing multiple myeloma, and (ii) IL-6 receptor expressing leukemia, in a human patient, comprising administering to the patient an effective amount of a composition comprising an NK cell and an antibody that neutralizes IL-6.
10 . The method of claim 9 , wherein the antibody is selected from the group consisting of siltuximab, olokizumab (CDP6038), elsilimomab, BMS-945429 (ALD518), MH-166, and sirukumab (CNTO 136).
11 . The method of claim 9 , wherein the NK cell is KHYG-1.
12 . A method of treating cancer comprising administering to a patient an effective amount of (a) an NK cell, and (b) an IL-6 antagonist.
13 . The method of claim 12 , wherein the NK cell and the IL-6 antagonist are administered separately.
14 . The method of claim 12 , wherein the patient is pretreated with an IL-6 antagonist before administration of an NK cell.
15 . The method of claim 12 , wherein the antagonist is an IL-6 antibody selected from the group consisting of siltuximab, olokizumab (CDP6038), elsilimomab, BMS-945429 (ALD518), MH-166, and sirukumab (CNTO 136).
16 . The method of claim 12 , wherein the cancer is a blood cancer selected from the group consisting of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CIVIL), hairy cell leukemia, T-cell prolymphocytic leukemia, large granular lymphocytic leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, including T-cell lymphomas and B-cell lymphomas, asymptomatic myeloma, smoldering multiple myeloma (SMM), multiple myeloma (MM), and light chain myeloma.
17 . A composition comprising an NK cell and an IL-6 antagonist.
18 . The composition of claim 17 , wherein the NK cell is KHYG-1.
19 . The composition of claim 17 , wherein the IL-6 antagonist is an antibody that neutralizes IL-6.
20 . The composition of claim 16 , wherein the IL-6 antagonist is an IL-6 antibody selected from the group consisting of siltuximab, olokizumab (CDP6038), elsilimomab, BMS-945429 (ALD518), MH-166, and sirukumab (CNTO 136).