B7-H4 antibodies and methods and use thereof
The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to human B7-H4. The anti-B7-H4 antibodies or antigen-binding fragments thereof are useful, for example in detecting B7-H4. Immunohistochemistry (IHC) can be used to detect B7-H4. The present disclosure also provides methods for treating cancer wherein increased B7-H4 has been detected, by administering a therapeutic anti-B7-H4 antibody or antigen-binding fragment thereof.
1. An isolated antibody or antigen-binding fragment thereof that specifically binds to human B7-H4, comprising a heavy chain variable region (VH) complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO:22, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:23, a VH CDR3 comprising the amino acid sequence of SEQ ID NO:24, a light chain variable region (VL) CDR1 comprising the amino acid sequence of SEQ ID NO:25, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:26, 27, or 28, and a VL CDR3 sequence comprising the amino acid sequence of SEQ ID NO:29.
2. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO:6, 7, or 8 and/or a VL comprising the amino acid sequence of SEQ ID NO:9, 10, or 11.
3. An isolated antibody or antigen-binding fragment thereof that specifically binds to human B7-H4, comprising a heavy chain variable region and a light chain variable region comprising the amino acid sequences of:
(a) SEQ ID NOs:6 and 9, respectively;
(b) SEQ ID NOs:6 and 10, respectively;
(c) SEQ ID NOs:6 and 11, respectively;
(d) SEQ ID NOs:7 and 9, respectively;
(e) SEQ ID NOs:7 and 10, respectively;
(f) SEQ ID NOs:7 and 11, respectively;
(g) SEQ ID NOs:8 and 9, respectively;
(h) SEQ ID NOs:8 and 10, respectively; or
(i) SEQ ID NOs:8 and 11, respectively.
4. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain and a light chain comprising the amino acid sequences of:
(a) SEQ IDNOs:16 and 19, respectively;
(b) SEQ ID NOs: 16 and 30, respectively;
(c) SEQ IDNOs:16 and 31, respectively;
(d) SEQ IDNOs:17 and 19, respectively;
(e) SEQ ID NOs: 17 and 30, respectively;
(f) SEQ ID NOs: 17 and 31, respectively;
(g) SEQ IDNOs:18 and 19, respectively;
(h) SEQ ID NOs: 18 and 30, respectively;
(i) SEQ IDNOs:18 and 31, respectively;
(j) SEQ ID NOs: 89 and 19, respectively;
(k) SEQ ID NOs: 90 and 19, respectively; or
(l) SEQ ID NOs: 91 and 19, respectively.
5. The antibody or antigen binding fragment thereof of claim 1 , which is an antigen binding fragment, wherein the antigen binding fragment comprises a Fab, Fab′, F(ab′) 2 , single chain Fv (scFv), disulfide linked Fv, minibody, F(ab1) 3 , diabody, (scFv) 2 , or scFv-Fc.
6. The antibody or antigen-binding fragment thereof of claim 1 , further comprising a detectable label.
7. An isolated polynucleotide comprising a nucleic acid molecule encoding the heavy chain variable region and the light chain variable region of the antibody or antigen-biding fragment thereof of claim 2 .
8. An isolated polynucleotide comprising a nucleic acid molecule encoding the heavy chain variable region of the antibody or antigen-binding fragment thereof of claim 4 and the light chain variable region of the antibody or antigen-binding fragment thereof of claim 4 .
9. An isolated vector comprising the polynucleotide of claim 8 .
10. A host cell comprising the vector of claim 9 .
11. A method of producing an antibody or antigen-binding fragment thereof that specifically binds to human B7-H4 comprising culturing the host cell of claim 10 so that the nucleic acid molecule is expressed and the antibody or antigen-biding fragment thereof is produced.
12. A kit comprising the antibody or antigen-binding fragment thereof of claim 1 and a) a detection reagent, b) a B7-H4 antigen, c) a therapeutic anti-B7-H4 antibody, or d) a combination of any of (a) through (c).
13. A method for detecting B7-H4 in a sample comprising contacting the sample with the antibody or antigen-binding fragment thereof of claim 1 .
14. The method of claim 13 , wherein the sample is obtained from a cancer in a subject.
15. The method of claim 14 , wherein the cancer is selected from the group consisting of breast cancer, ductal carcinoma, endometrial carcinoma, ovarian cancer, non-small cell lung cancer, pancreatic cancer, thyroid cancer, kidney cancer and bladder cancer.
16. The method of claim 14 , further comprising administering a therapeutic anti-B7-H4 antibody or antigen-binding fragment thereof to the subject after B7-H4 has been detected.
17. The method of claim 16 , wherein the therapeutic antibody or antigen-binding fragment comprises (i) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:54 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:55 or (ii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:64 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:65.