Anti-B7-H6 antibody, fusion proteins, and methods of using the same

1. An isolated antibody, or antigen binding fragment of the antibody, which specifically binds to B7 homolog 6 (B7-H6) comprising:

(a) a heavy chain variable region (VH) comprising,

(i) a complementarity-determining region 1 (CDR1) of SEQ ID NO: 5,

(ii) a complementarity-determining region 2 (CDR2) of SEQ ID NO: 6, and

(iii) a complementarity-determining region 3 (CDR3) of SEQ ID NO: 7; and

(b) a light chain variable region (V L) comprising,

(i) a CDR1 of SEQ ID NO: 8,

(ii) a CDR2 of SEQ ID NO: 9, and

(iii) a CDR3 of SEQ ID NO: 10.

2. The isolated antibody, or antigen binding fragment of the antibody according to claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 3 and the VL comprises the amino acid sequence of SEQ ID NO: 4.

3. The isolated antibody, or antigen binding fragment of the antibody according to claim 1 , which comprises an antigen binding fragment of the antibody selected from the group consisting of a F(ab), a F(ab) 2 , a F(ab′) 2 , a Fv, a dsFv, a scFv, a scFv-Fc, a (scFv) 2 , and a diabody.

4. The isolated antibody, or antigen binding fragment of the antibody according to claim 1 , which is conjugated to a synthetic molecule, optionally wherein the synthetic molecule is a label, a contrast agent, a magnetic nanoparticle, a cytotoxic agent, a cytostatic agent, an anti-angiogenic agent, or a radioisotope.

5. The isolated antibody, or antigen binding fragment of the antibody according to claim 1 , which is chimeric or humanized.

6. The isolated antibody, or antigen binding fragment of the antibody according to claim 1 , which is synthetic, optionally recombinant.

7. The isolated antibody, or antigen binding fragment of the antibody according to claim 1 , wherein the antibody is of an IgM, IgD, IgG, IgE, or IgE isotype.

8. A bispecific compound comprising:

(a) an antigen-binding fragment of an anti-B7-H6 antibody, wherein the antigen-binding fragment comprises:

(a-1) a heavy chain variable region (VH) comprising,

(i) a CDR1 of SEQ ID NO: 5,

(ii) a CDR2 of SEQ ID NO: 6, and

(iii) a CDR3 of SEQ ID NO: 7; and

(a-2) a light chain variable region (V L) comprising,

(i) a CDR1 of SEQ ID NO: 8,

(ii) a CDR2 of SEQ ID NO: 9, and

(iii) a CDR3 of SEQ ID NO: 10; and

(b) an antigen-binding fragment of an anti-CD3 antibody.

9. The bispecific compound according to claim 8 , wherein the antigen-binding fragment of an anti-B7-H6 antibody and/or the antigen-binding fragment of an anti-CD3 antibody is humanized.

10. The bispecific compound according to claim 8 , wherein in (a) the VH comprises the amino acid sequence of SEQ ID NO: 3 and/or the VL comprises the amino acid sequence of SEQ ID NO: 4.

11. The bispecific compound according to claim 8 , which when administered to a subject having a B7-H6 expressing tumor elicits interferon gamma secretion.

12. The bispecific compound according to claim 8 , which when administered to a subject having a B7-H6 expressing tumor elicits an antitumor response.

13. The bispecific compound according to claim 8 , wherein the antigen-binding fragment of an anti-CD3 antibody comprises:

(b-1) a heavy chain variable region (VH) comprising

(i) a CDR1 of SEQ ID NO: 15,

(ii) a CDR2 of SEQ ID NO: 16, and

(iii) a CDR3 of SEQ ID NO: 17; and

(b-2) a light chain variable region (V L) comprising

(i) a CDR1 of SEQ ID NO: 18,

(ii) a CDR2 of SEQ ID NO: 19, and

(iii) a CDR3 of SEQ ID NO: 20.

14. The bispecific compound according to claim 8 , which is a bispecific T cell-engager, a dual affinity retargeting agent, a diabody, or a conjugated Fab dimer.

15. The bispecific compound according to claim 8 , wherein the antigen-binding fragment of an anti-B7-H6 antibody and the antigen-binding fragment of an anti-CD3 antibody are linked by a linker.

16. The bispecific compound according to claim 8 , wherein:

(a) the antigen-binding fragment of an anti-B7-H6 antibody is an anti-B7-H6 scFv; and

(b) the antigen-binding fragment of an anti-CD3 antibody is an anti-CD3 scFv.

17. The bispecific compound according to claim 16 , wherein the anti-B7-H6 scFv and the anti-CD3 scFv are fused by a linker.

18. The bispecific compound according to claim 8 , comprising:

(A) a first polypeptide comprising the VH specific for B7-H6 and a VL specific for CD3; and

(B) a second polypeptide comprising the VL specific for B7-H6 and a VH specific for CD3, wherein:

(a) the VH specific for B7-H6 and the VL specific for B7-H6 interact to form said antigen-binding fragment of an anti-B7-H6 antibody; and

(b) the VH specific for CD3 and the VL specific for CD3 interact to form said antigen-binding fragment of an anti-CD3 antibody.

19. A pharmaceutical composition comprising:

(I) the isolated antibody, or antigen binding fragment of the antibody according to claim 1 ; and

(II) a pharmaceutically acceptable carrier.

20. A pharmaceutical composition comprising:

(I) the bispecific compound according to claim 8 ; and

(II) a pharmaceutically acceptable carrier.