Anti-B7-H3 antibodies and diagnostic uses thereof
Provided herein are B7-H3 antibodies, fragments of such antibodies, and compositions comprising the same. The antibodies, antibody fragments and compositions are useful in a number of analytical methods, including immunohistochemical and immunocytochemical detection and analysis of B7-H3. Also provided herein are isolated peptides, compositions, and fusion proteins containing immunogenic determinants for said B7-H3 antibodies, animals immunized with the peptides and fusion proteins, isolated B cells obtained from the animals, and hybridomas made from the isolated B cells.
1. An isolated antibody or an antigen binding fragment thereof, said antibody or antigen-binding fragment thereof comprising a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence, wherein the antibody binds to an epitope of human B7-H3 comprising the amino acid sequence KHSDSKEDDGQEIA (SEQ ID NO: 1), wherein:
(a) the HC comprises a CDR3 sequence of RAPVVSTSMTFNI (SEQ ID NO: 4) or TVVGGWGYALDL (SEQ ID NO: 10); or
(b) the LC comprises a CDR3 sequence QGEFTCSGADCGA (SEQ ID NO: 7); or
(c) the HC comprises a CDR3 sequence of RAPVVSTSMTFNI (SEQ ID NO: 4) or TVVGGWGYALDL (SEQ ID NO: 10), and wherein the LC comprises a CDR3 sequence QGEFTCSGADCGA (SEQ ID NO: 7).
2. The antibody of claim 1 , wherein the HC further comprises a CDR2 sequence of GSGKRGNPYYASWAKS (SEQ ID NO: 3) or CIYAGSSLNTYYAPWAKG (SEQ ID NO: 9).
3. The antibody of claim 1 , wherein the HC further comprises a CDR1 sequence of SYGVS (SEQ ID NO: 2) or SSYWIC (SEQ ID NO: 8).
4. The antibody of claim 1 , wherein the LC further comprises a CDR2 sequence EASTLAS (SEQ ID NO: 6).
5. The antibody of claim 1 , wherein the LC further comprises a CDR1 sequence QASQSVYNNKNLS (SEQ ID NO: 5).
6. The antibody of claim 1 , wherein:
the HC comprises
(a) a HC CDR1 comprising the amino acid sequence SYGVS (SEQ ID NO: 2); and/or
(b) a HC CDR2 comprising the amino acid sequence GSGKRGNPYYASWAKS (SEQ ID NO: 3); and/or
(c) a HC CDR3 comprising the amino acid sequence RAPVVSTSMTFNI (SEQ ID NO: 4); and/or
the LC comprises
(a) a LC CDR1 comprising the amino acid sequence QASQSVYNNKNLS (SEQ ID NO: 5); and/or
(b) a LC CDR2 comprising the amino acid sequence EASTLAS (SEQ ID NO: 6); and/or
(c) a LC CDR3 comprising the amino acid sequence QGEFTCSGADCGA (SEQ ID NO: 7).
7. The antibody claim 1 , wherein:
the HC comprises
(a) a HC CDR1 comprising the amino acid sequence SSYWIC (SEQ ID NO: 8); and/or
(b) a HC CDR2 comprising the amino acid sequence CIYAGSSLNTYYAPWAKG (SEQ ID NO: 9); and/or
(c) a HC CDR3 comprising the amino acid sequence TVVGGWGYALDL (SEQ ID NO: 10); and/or
the LC comprises
(a) a LC CDR1 comprising the amino acid sequence QASQSVYNNKNLS (SEQ ID NO: 5); and/or
(b) a LC CDR2 comprising the amino acid sequence EASTLAS (SEQ ID NO: 6); and/or
(c) a LC CDR3 comprising the amino acid sequence QGEFTCSGADCGA (SEQ ID NO: 7).
8. The antibody of claim 1 , wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of SEQ ID NOS: 11 or 13.
9. The antibody of claim 1 , wherein the LC immunoglobulin variable domain sequence comprises the amino acid sequence of SEQ ID NOS: 12 or 14.
10. The antibody of claim 1 , wherein the antibody is selected from the group consisting of: a monoclonal antibody, a chimeric antibody or a humanized antibody.
11. The antigen binding fragment of claim 1 , wherein the antigen binding fragment is selected from the group consisting of Fab, F(ab′)2, Fab′, scF v , and F v .
12. A composition comprising the antibody or antigen binding fragment of claim 1 , and a carrier.
13. A composition comprising the antibody or antigen binding fragment of claim 1 , bound to a peptide comprising SEQ ID NO: 1.
14. The composition of claim 13 , wherein the peptide is a human B7-H3 protein.
15. The composition of claim 13 , wherein the peptide is associated with a cell.
16. The composition of claim 13 , wherein the peptide is bound to a solid support.
17. The composition of claim 13 , wherein the peptide is disposed in a solution.
18. The composition of claim 13 , wherein the peptide is associated with a matrix.
19. A method of detecting B7-H3 in a biological sample comprising contacting the sample with the antibody or antigen binding fragment of claim 1 , and detecting a complex formed by the binding of the antibody or antigen binding fragment to B7-H3.
20. The method of claim 19 , wherein the sample comprises a cell sample or a tissue sample.
21. The method of claim 20 , wherein the sample is obtained from a subject that is diagnosed as having, suspected as having, or at risk of having cancer.
22. The method of claim 21 , wherein the cancer is selected from the group consisting of bladder transitional cell carcinoma, renal cell carcinoma, and lung squamous cell carcinoma.
23. The method of claim 19 , wherein the detection comprises one or more of immunocytochemistry (ICC), immunohistochemistry (IHC), Western blotting, flow cytometry or ELISA.
24. A kit for detecting B7-H3 comprising the antibody or antigen binding fragment of claim 1 , and instructions for use.