Antibodies that bind human CD27 and uses thereof
Isolated monoclonal antibodies which bind to human CD27 and related antibody-based compositions and molecules are disclosed. Also disclosed are therapeutic and diagnostic methods for using the antibodies.
1. An isolated monoclonal antibody which binds to human CD27, wherein the antibody comprises:
a heavy chain variable region CDR1 comprising SEQ ID NO: 38;
a heavy chain variable region CDR2 comprising SEQ ID NO: 39;
a heavy chain variable region CDR3 comprising SEQ ID NO: 40;
a light chain variable region CDR1 comprising SEQ ID NO: 44;
a light chain variable region CDR2 comprising SEQ ID NO: 45; and
a light chain variable region CDR3 comprising SEQ ID NO: 46.
2. An isolated monoclonal antibody which binds to human CD27 and comprises a heavy chain variable region comprising SEQ ID NO:37.
3. An isolated monoclonal antibody which binds to human CD27 and comprises a light chain variable region comprising SEQ ID NO:43.
4. An isolated monoclonal antibody which binds to human CD27 and comprises a heavy chain variable region comprising SEQ ID NO:37 and a light chain variable region comprising SEQ ID NO:43.
5. An isolated monoclonal antibody that binds human CD27, wherein the antibody comprises a heavy chain variable region and a light chain variable region encoded by nucleotide sequences set forth in SEQ ID NOs:35 and 41, respectively.
6. A composition comprising the antibody of claim 1 and a carrier.
7. The composition of claim 6 , further comprising an adjuvant.
8. The composition of claim 6 , further comprising an immunostimulatory agent.
9. The composition of claim 8 , wherein the immunostimulatory agent is selected from the group consisting of CD40 ligand, FLT 3 ligand, cytokines, colony-stimulating factors, an anti-CTLA-4 antibody, LPS (endotoxin), ssRNA, dsRNA, Bacille Calmette-Guerin (BCG), Levamisole hydrochloride, intravenous immune globulins and a Toll-like Receptor (TLR) agonist.
10. The composition of claim 9 , wherein the Toll-like Receptor agonist is selected from the group consisting of a TLR3 agonist, a TLR4 agonist, a TLR5 agonist, a TLR7 agonist, a TLR8 agonist, and a TLR 9 agonist.
11. The composition of claim 6 , further comprising an immunosuppressive agent.
12. The composition of claim 6 , further comprising another antibody.
13. The composition of claim 6 , further comprising an antigen.
14. The composition of claim 13 , wherein the antigen comprises a tumor antigen, allergen or an autoantigen.
15. The composition of claim 14 , wherein the tumor antigen is selected from the group consisting of βhCG, gp100 or Pme117, HER2/neu, WT1, mesothelin, CEA, gp100, MART1, TRP-2, melan-A, NY-ESO-1, NY-BR-1, NY-CO-58, MN (gp250), idiotype, MAGE-1, MAGE-3, MAGE-A3, Tyrosinase, Telomerase, SSX2 antigens, MUC-1 antigens, and germ cell derived tumor antigens.
16. A bispecific antibody comprising the antibody of claim 1 linked to a second molecule having a binding specificity which is different from the antibody.
17. The bispecific molecule of claim 16 , wherein the second molecule binds to a T cell receptor.
18. The bispecific molecule of claim 17 , wherein the T cell receptor is selected from the group consisting of CD3, CD40 and CD25.
19. The bispecific molecule of claim 16 , wherein the second molecule binds to an NK receptor.