Compositions and methods concerning combinations of immunologic inhibitors for the treatment of cancer
Aspects herein relate to combinations of inhibitors useful in the treatment of cancer, and methods of treating cancer using such combinations. In some embodiments, the methods involve the use of a combination of at least two of the following: an inhibitor of indoleamine-2,3-dioxygenase (IDO), an inhibitor of the PD-L1/PD-1 pathway, an inhibitor of CTLA-4, an inhibitor of CD25, or IL-7.
1 . A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an inhibitor of CTLA-4 and one of: an inhibitor of indoleamine-2,3-dioxygenase (IDO) or an inhibitor of the PD-L1/PD-1 pathway, wherein the CTLA-4 inhibitor comprises ipilimumab; tremelimumab or UC10-4F10-11; and wherein the IDO inhibitor is:
or a combination thereof.
2 . The method of claim 1 , wherein the method comprises administering the inhibitor of IDO and the inhibitor of CTLA-4.
3 . The method of claim 1 , wherein the method comprises administering the inhibitor of the PD-L1/PD-1 pathway and the inhibitor of CTLA-4.
4 . The method of claim 1 , wherein the inhibitor of the PD-L1/PD-1 pathway is an anti-PD-L1 antibody or an anti-PD-1 antibody.
5 . The method of claim 4 , wherein the anti-PD-L1 antibody is BMS-936559, MPDL3280A, BMS-936558, MK-3475, CT-011, or MEDI4736.
6 . The method of claim 1 , wherein the anti-CTLA-4 inhibitor is ipilimumab.
7 . The method of claim 1 , wherein treating cancer is further defined as reducing the size of a tumor of the cancer or inhibiting growth of a tumor of the cancer.
8 . The method of claim 1 , wherein the cancer is melanoma, cervical cancer, breast cancer, ovarian cancer, prostate cancer, testicular cancer, urothelial carcinoma, bladder cancer, non-small cell lung cancer, small cell lung cancer, sarcoma, colorectal adenocarcinoma, gastrointestinal stromal tumors, gastroesophageal carcinoma, colorectal cancer, pancreatic cancer, kidney cancer, hepatocellular cancer, malignant mesothelioma, leukemia, lymphoma, myelodysplastic syndrome, multiple myeloma, transitional cell carcinoma, neuroblastoma, plasma cell neoplasms, Wilm's tumor, or hepatocellular carcinoma.
9 . The method of claim 8 , wherein the cancer is melanoma.
10 . The method of claim 1 , wherein the inhibitor of CTLA-4 and the one of the inhibitor of indoleamine-2,3-dioxygenase (IDO) or the inhibitor of the PD-L1/PD-1 pathway are administered to the subject at least two, three, four, five, six, seven, eight, nine or ten times.
11 . The method of claim 1 , wherein said subject is further administered a distinct cancer therapy.
12 . The method of claim 11 , wherein said distinct cancer therapy comprises surgery, radiotherapy, chemotherapy, toxin therapy, immunotherapy, cryotherapy or gene therapy.
13 . The method of claim 1 , wherein the cancer is a chemotherapy-resistant or radio-resistant cancer.
14 . The method of claim 1 , wherein the subject is administered at least 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, or 300 mg/kg of the CTLA-4 inhibitor and the one of the IDO inhibitor or the PD-L1/PD-1 inhibitor.
15 . The method of claim 1 , wherein the CTLA-4 inhibitor is ipilimumab and the IDO inhibitor is
16 . The method of claim 8 , wherein the CTLA-4 inhibitor is ipilimumab and the IDO inhibitor is
17 . The method of claim 2 , further comprising administering to the subject a therapeutically effective amount of an inhibitor of the PD-L1/PD-1 pathway.
18 . The method of claim 3 , further comprising administering to the subject a therapeutically effective amount of an inhibitor of IDO, wherein the inhibitor of IDO inhibitor is:
or a combination thereof.