Anti-galectin-9 antibodies and uses thereof
Disclosed herein are anti-Galectin-9 antibodies and methods of using such for inhibiting a signaling pathway mediated by Galectin-9 or eliminating pathologic cells expressing Galectin-9. Such anti-Galectin-9 antibodies may also be used to diagnose and/or to treat diseases associated with Galectin-9, such as autoimmune diseases and solid tumors.
1. A method for treating a galectin-9 expressing hematological malignancy in a human subject, comprising administering to the human subject an effective amount of a pharmaceutical composition comprising an antibody that binds human galectin-9, wherein the antibody comprises:
(a) a heavy chain complementarity determining region 1 (CDR1) set forth as SEQ ID NO: 361, a heavy chain complementary determining region 2 (CDR2) set forth as SEQ ID NO: 388, and a heavy chain complementary determining region 3 (CDR3) set forth as SEQ ID NO: 406 and
(b) a light chain complementarity determining region 1 (CDR1) set forth as SEQ ID NO: 328, a light chain complementary determining region 2 (CDR2) set forth as SEQ ID NO: 329, and a light chain complementary determining region 3 (CDR3) set forth as SEQ ID NO: 352.
2. The method of claim 1 , wherein the antibody is a full-length antibody or an antigen-binding fragment thereof.
3. The method of claim 1 , wherein the antibody is an IgG molecule.
4. The method of claim 3 , wherein the antibody is a IgG1 or an IgG4 antibody.
5. The method of claim 1 , wherein the antibody comprises a V H set forth as SEQ ID NO: 55 and a V L set forth as SEQ ID NO: 54.
6. The method of claim 2 , wherein the antibody is a full-length antibody, which comprises a heavy chain constant region set forth as SEQ ID NO: 422, and light chain constant region set forth as SEQ ID NO: 418.
7. The method of claim 1 , wherein the antibody comprises a heavy chain set forth as SEQ ID NO: 316 and a light chain set forth as SEQ ID NO: 108.
8. The method of claim 1 , wherein the hematological malignancy is selected from the group consisting of a leukemia, a lymphoma, multiple myeloma, a myelodysplastic syndrome, and a myeloproliferative neoplasm.
9. The method of claim 8 , wherein the hematological malignancy is a leukemia or a lymphoma.
10. The method of claim 8 , wherein the hematological malignancy is a leukemia, which is selected from the group consisting of myelogenous leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, and acute lymphoblastic leukemia.
11. The method of claim 10 , wherein the leukemia is acute myelogenous leukemia.
12. The method of claim 8 , wherein the hematological malignancy is a lymphoma, which is selected from the group consisting of AIDS-related lymphoma, Burkitt lymphoma, cutaneous T cell lymphoma, Hodgkin lymphoma, Non-Hodgkin lymphoma, and primary central nervous system lymphoma.
13. The method of claim 12 , wherein the lymphoma is Non-Hodgkins lymphoma.
14. The method of claim 1 , wherein the method further comprises subjecting the human subject to a radiation therapy, an immunotherapy, a chemotherapy, or combinations thereof.
15. The method of claim 14 , wherein the human subject is treated by the immunotherapy, which comprises a checkpoint inhibitor.
16. The method of claim 15 , wherein the checkpoint inhibitor is an anti-PD-1 antibody or an anti-TIM-3 antibody.
17. The method of claim 14 , wherein the human subject is treated by the chemotherapy, which comprises a chemotherapeutic agent selected from the group consisting of a pyrimidine analog, a purine analog, a folate antagonist or related inhibitor, an anti-proliferative/anti-mitotic agent, vincristine, vinblastine, nocodazole, epothilone, navelbine, etoposide, teniposide, methotrexate, and cytarabine.