Antibody therapeutics that bind STAT3
The present disclosure provides anti-STAT3 antibodies, and antigen-binding portions thereof. In certain embodiments, the antibodies or fragments thereof, are used for the treatment of cancer.
1. An isolated anti-Signal Transducer and Activator of Transcription 3 (STAT3) antibody, or an antigen-binding fragment thereof, comprising
a heavy chain variable domain comprising a CDR3 domain comprising an amino acid sequence as set forth in SEQ ID NO: 9, a CDR2 domain comprising an amino acid sequence as set forth in SEQ ID NO: 8, and a CDR1 domain comprising an amino acid sequence as set forth in SEQ ID NO: 7; and
a light chain variable domain comprising a CDR3 domain comprising an amino acid sequence as set forth in SEQ ID NO: 12, a CDR2 domain comprising an amino acid sequence as set forth in SEQ ID NO: 11, and a CDR1 domain comprising an amino acid sequence as set forth in SEQ ID NO: 10.
2. The antibody, or antigen-binding fragment thereof of claim 1 , wherein the heavy chain variable domain comprises an amino acid sequence as set forth in SEQ ID NO: 1, and the light chain variable domain comprises an amino acid sequence as set forth in SEQ ID NO: 2.
3. An isolated anti-STAT3 antibody, or an antigen-binding fragment thereof, comprising
a heavy chain variable domain comprising a CDR3 domain comprising an amino acid sequence as set forth in SEQ ID NO: 15, a CDR2 domain comprising an amino acid sequence as set forth in SEQ ID NO: 14, and a CDR1 domain comprising an amino acid sequence as set forth in SEQ ID NO: 13; and
a light chain variable domain comprising a CDR3 domain comprising an amino acid sequence as set forth in SEQ ID NO: 18, a CDR2 domain comprising an amino acid sequence as set forth in SEQ ID NO: 17, and a CDR1 domain comprising an amino acid sequence as set forth in SEQ ID NO: 16.
4. The antibody, or antigen-binding fragment thereof of claim 3 , wherein the heavy chain variable domain comprises an amino acid sequence as set forth in SEQ ID NO: 3, and the light chain variable domain comprises an amino acid sequence as set forth in SEQ ID NO: 4.
5. The anti-STAT3 antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody has a K D of 1×10 −6 M or less.
6. The anti-STAT3 antibody, or antigen-binding fragment thereof, of claim 3 , wherein the antibody has a K D of 1×10 −6 M or less.
7. The anti-STAT3 antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antigen-binding fragment is a Fab fragment or an scFv.
8. The anti-STAT3 antibody, or antigen-binding fragment thereof, of claim 3 , wherein the antigen-binding fragment is a Fab fragment or an scFv.
9. The anti-STAT3 antibody, or an antigen-binding fragment thereof, of claim 1 , which is conjugated to an intracellular delivery compound.
10. The anti-STAT3 antibody, or an antigen-binding fragment thereof, of claim 3 , which is conjugated to an intracellular delivery compound.
11. A method for treating a subject having a STAT3 expressing cancer, the method comprising administering an effective amount of the anti-STAT3 antibody, or antigen-binding fragment thereof, of claim 1 to the subject.
12. The method of claim 11 , wherein the cancer is a solid tumor.
13. The method of claim 11 , wherein the cancer is selected from the group consisting of melanoma, glioma, medulloblastoma, renal cell carcinoma, pancreatic adenocarcinoma, ovarian carcinoma, rhabdomyosarcoma, osteosarcoma, glioblastoma, breast, pancreas, ovarian, prostate, lung, liver, colon, colorectal, gastric, head, neck, and kidney.
14. The method of claim 11 , wherein the cancer is a hematological cancer.
15. The method of claim 14 , wherein the hematological cancer is selected from the group consisting of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), hairy cell leukemia, chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), megakaryocytic leukemia and large granular lymphocyte leukemia.
16. A method for treating a subject having a STAT3 expressing cancer, the method comprising administering an effective amount of the anti-STAT3 antibody, or antigen-binding fragment thereof, of claim 3 to the subject.
17. A method for treating a subject having an autoimmune disease, the method comprising administering an effective amount of the anti-STAT3 antibody, or antigen-binding fragment thereof, of claim 1 to the subject.
18. The method of claim 17 , wherein the autoimmune disease is selected from the group consisting of multiple sclerosis, Crohn's disease, certain bacterially induced colitis, arthritis, lupus, diabetes, asthma, inflammatory bowel disease, scleroderma, and vasculitis.
19. A method for treating a subject having an autoimmune disease, the method comprising administering an effective amount of the anti-STAT3 antibody, or antigen-binding fragment thereof, of claim 3 to the subject.
20. A pharmaceutical composition comprising the anti-STAT3 antibody, or antibody fragment of claim 1 , and a pharmaceutically acceptable carrier.
21. A pharmaceutical composition comprising the anti-STAT3 antibody, or antibody fragment of claim 3 , and a pharmaceutically acceptable carrier.