THERAPEUTIC COMBINATIONS COMPRISING ANTI-CD73 ANTIBODIES AND USES THEREOF
The present invention provides therapeutic combinations featuring anti-CD73 antibodies (e.g., MEDI9447) and A2A receptor inhibitors and methods of using such combinations for reducing tumor-mediated immunosuppression.
1 . A method of inhibiting tumor growth in a subject comprising administering an anti-CD73 antibody, or an antigen-binding fragment thereof, and an A2A receptor inhibitor for inhibiting tumor growth to the subject.
2 . A method of increasing an anti-tumor immune response comprising administering an anti-CD73 antibody, or an antigen-binding fragment thereof, and an A2A receptor inhibitor to a subject in need thereof.
3 . A method of treating a tumor in a subject comprising administering an anti-CD73 antibody, or an antigen-binding fragment thereof, and an A2A receptor inhibitor for treating a tumor to a subject.
4 . The method any one of claims 1 - 3 , wherein the anti-CD73 antibody is MEDI9447 or an antigen-binding fragment thereof.
5 . The method of any one of claims 1 - 3 , wherein the anti-CD73 antibody is Phen0203 hIgG1 or an antigen-binding fragment thereof.
6 . The method of any one of claims 1 - 3 , wherein the A2A receptor inhibitor is SCH58261.
7 . The method of any one of claims 1 - 3 , wherein the anti-CD73 antibody is MEDI9447 or an antigen-binding fragment thereof and the A2A receptor inhibitor is SCH58261.
8 . The method of any one of claims 1 - 3 , wherein the anti-CD73 antibody is Phen0203 hIgG1 or an antigen-binding fragment thereof and the A2A receptor inhibitor is SCH58261.
9 . The method of any one of claims 1 - 3 , wherein the anti-CD73 antibody or antigen-binding fragment thereof and the adenosine receptor inhibitor (A2ARi) are administered concurrently.
10 . The method of any one of claims 1 - 3 , wherein the anti-CD73 antibody or antigen-binding fragment thereof is administered prior to the adenosine receptor inhibitor (A2ARi).
11 . The method of any one of claims 1 - 3 , wherein the adenosine receptor inhibitor (A2ARi) is administered prior to the anti-CD73 antibody or antigen-binding fragment thereof.
12 . The method of any one of claims 1 - 3 , wherein the tumor is a breast cancer, hormonally mediated breast cancer, triple negative breast cancer, colon carcinoma, colorectal cancer, lung cancer, melanoma, non-small cell carcinoma, lymphoma, Hodgkin's and non-Hodgkin's lymphoma, Burkitt's lymphoma, and sarcoma.
13 . The method of any one of claims 1 - 3 , wherein said method results in an increase in overall survival as compared to the administration of any one of the anti-CD73 antibody or the A2A receptor inhibitor alone.
14 . The method of any one of claims 1 - 3 , wherein the said method induces or increases a tumor-specific immune response.
15 . The method of any one of claims 1 - 3 , wherein the said method reduces the immunosuppressive effects of a AMP/CD73/adenosine pathway.
16 . The method of any one of claims 1 - 3 , wherein the said method reduces metastasis or reduces the propensity of the tumor to metastasize relative to the administration of either the anti-CD73 antibody or the adenosine receptor inhibitor (A2ARi) alone.
17 . The method of any one of claims 1 - 3 , wherein the said method reduces the number of metastases within the subject.
18 . The method of any one of claims 1 - 3 , wherein the subject is a human patient.
19 . The method of any one of claims 1 - 3 , wherein the tumor is a CD73 overexpres sing tumor.
20 . The method of any one of claims 1 - 3 , wherein the cancer has a prometastatic phenotype.
21 . A kit for increasing anti-tumor activity, the kit comprising an anti-CD73 antibody or antigen-binding fragment thereof and an A2A receptor inhibitor.
22 . The kit of claim 21 , wherein the anti-CD73 antibody is MEDI9447 or an antigen-binding fragment thereof.
23 . The kit of claim 21 , wherein the anti-CD73 antibody is Phen0203 hIgG1 or an antigen-binding fragment thereof.
24 . The kit of claim 21 , wherein the A2A receptor inhibitor is SCH58261.
25 . The kit of claim 21 , wherein the anti-CD73 antibody is MEDI9447 or an antigen-binding fragment thereof and the A2A receptor inhibitor is SCH58261.
26 . The kit of claim 21 , wherein the anti-CD73 antibody is Phen0203 hIgG1 or an antigen-binding fragment thereof and the A2A receptor inhibitor is SCH58261.
27 . A pharmaceutical formulation comprising an effective amount an anti-CD73 antibody or antigen-binding fragment thereof and an A2A receptor inhibitor.
28 . The pharmaceutical formulation of claim 27 , wherein the anti-CD73 antibody is MEDI9447 or an antigen-binding fragment thereof.
29 . The pharmaceutical formulation of claim 27 , wherein the anti-CD73 antibody is Phen0203 hIgG1 or an antigen-binding fragment thereof.
30 . The pharmaceutical formulation of claim 27 , wherein the A2A receptor inhibitor is SCH58261.
31 . The pharmaceutical formulation of claim 27 , wherein the anti-CD73 antibody is MEDI9447 or an antigen-binding fragment thereof and the A2A receptor inhibitor is SCH58261.
32 . The pharmaceutical formulation of claim 27 , wherein the anti-CD73 antibody is Phen0203 hIgG1 or an antigen-binding fragment thereof and the A2A receptor inhibitor is SCH58261.