Antibodies that bind human cd27 and uses thereof

Abstract

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 . (canceled) 
     
     
         2 . An isolated monoclonal antibody which binds to human CD27, wherein the antibody respectively comprises heavy and light chain variable region sequences having at least 95% identity to:
 (a) SEQ ID NOs: 37 and 43;   (b) SEQ ID NOs: 49 and 55;   (c) SEQ ID NOs: 103 and 109;   (d) SEQ ID NOs: 85 and 91;   (e) SEQ ID NOs: 85 and 97;   (f) SEQ ID NOs: 25 and 31;   (g) SEQ ID NOs: 73 and 79;   (h) SEQ ID NOs: 7 and 13;   (i) SEQ ID NOs: 7 and 19; or   (j) SEQ ID NOs: 61 and 67.   
     
     
         3 . The antibody of  claim 2 , wherein the antibody comprises heavy and light chain variable region sequences having at least 95% identity, 96% identity, 97% identity, 98% identity, or 99% identity to SEQ ID NOs: 37 and 43, respectively. 
     
     
         4 . A composition comprising the antibody of  claim 2  and a carrier. 
     
     
         5 . The composition of  claim 4 , further comprising an adjuvant. 
     
     
         6 . The composition of  claim 4 , further comprising an immunostimulatory agent. 
     
     
         7 . The composition of  claim 6 , 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. 
     
     
         8 . The composition of  claim 7 , 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. 
     
     
         9 . The composition of  claim 4 , further comprising an immunosuppressive agent. 
     
     
         10 . The composition of  claim 4 , further comprising another antibody. 
     
     
         11 . The composition of  claim 4 , further comprising an antigen. 
     
     
         12 . The composition of  claim 11 , wherein the antigen comprises a tumor antigen, allergen, or an autoantigen. 
     
     
         13 . The composition of  claim 12 , wherein the tumor antigen is selected from the group consisting of βhCG, gp100 or Pmel17, 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. 
     
     
         14 . A bispecific antibody comprising the antibody of  claim 2  linked to a second molecule having a binding specificity which is different from the antibody. 
     
     
         15 . The bispecific molecule of  claim 14 , wherein the second molecule binds to a T cell receptor. 
     
     
         16 . The bispecific molecule of  claim 15 , wherein the T cell receptor is selected from the group consisting of CD3, CD40 and CD25. 
     
     
         17 . The bispecific molecule of  claim 14 , wherein the second molecule binds to an NK receptor.