Antibodies to human b7x for treatment of metastatic cancer

Abstract

Methods are provided for treating metastatic cancer in patients having metastatic cancer or for preventing metastasis in cancer patients at risk for metastasis comprising administering to the patient an antibody to B7x, or an active antibody fragment that binds B7x, in an amount effective to treat or prevent metastasis.

1 . A method for treating metastatic cancer in a patient having metastatic cancer or for preventing metastasis in a cancer patient at risk for metastasis comprising administering to the patient a monoclonal antibody, or a fragment thereof, that binds to B7x, in an amount effective to treat or prevent metastasis in a patient, wherein the antibody or antibody fragment binds to amino acid residues 35-148 of SEQ ID NO:1. 
     
     
         2 . The method of  claim 1  comprising determining the level of B7x expression in a tumor sample from the patient, and if B7x is over-expressed in the tumor sample compared to healthy tissue, administering to the patient an antibody to B7x, or an antibody fragment that binds B7x, in an amount effective to treat or prevent metastasis in a patient. 
     
     
         3 . The method of  claim 1 , wherein the patient has metastatic cancer. 
     
     
         4 . The method of  claim 1 , wherein the patient is a cancer patient at risk for metastasis. 
     
     
         5 . The method of  claim 1 , wherein the cancer is a cancer of the skin, breast, pancreas, prostate, ovary, kidney, esophagus, gastrointestional tract, colon, brain, liver, lung, head and/or neck. 
     
     
         6 - 7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the antibody is an IgG monoclonal antibody. 
     
     
         9 . The method of  claim 1 , wherein the antibody is an IgG1 monoclonal antibody. 
     
     
         10 . The method of  claim 1 , wherein administration of the antibody or antibody fragment decreases the number of tumor nodules in the patient. 
     
     
         11 . The method of  claim 1 , wherein administration of the antibody or antibody fragment reduces the number of metastases. 
     
     
         12 . The method of  claim 1 , wherein administration of the antibody or antibody fragment prevents the occurrence or reoccurrence of metastasis. 
     
     
         13 . The method of  claim 1 , wherein administration of the antibody or antibody fragment increases the patient's survival time. 
     
     
         14 . The method of  claim 1 , wherein the antibody or antibody fragment does not include an antibody-partner molecule conjugate. 
     
     
         15 . The method of  claim 1 , wherein the antibody or antibody fragment is the sole therapeutic anti-cancer agent administered to the patient. 
     
     
         16 . The method of  claim 1 , wherein the antibody or antibody fragment is administered in combination with another anti-cancer agent. 
     
     
         17 - 18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein administration of the antibody or antibody fragment prevents the reoccurrence of a tumor in the patient. 
     
     
         20 . A method for preventing reoccurrence of a tumor in a patient comprising administering to the patient a monoclonal antibody, or a fragment thereof, that binds B7x, in an amount effective to prevent reoccurrence of a tumor in a patient, wherein the antibody or antibody fragment binds to amino acid residues 35-148 of SEQ ID NO:1. 
     
     
         21 . A method of producing a monoclonal antibody to B7x comprising:
 immunizing a B7x knockout mouse with a B7x-Ig fusion protein,   generating a hybridoma from spleen cells from the mouse, and   testing supernatant from the hybridoma for its ability to react with immobilized B7x-Ig or a cell line expressing B7x, but not with control Igs or cell lines expressing other B7 family members, to identify a monoclonal antibody to B7x.   
     
     
         22 . The method of  claim 21  further comprising generating a B7x knockout mouse. 
     
     
         23 . The method of  claim 21  further comprising purifying the antibody from the supernatant. 
     
     
         24 . A method of screening monoclonal antibodies to B7x to identify an antibody that inhibits tumor growth in vivo, the method comprising
 injecting tumor cells expressing B7x on their cell surface into a mouse to induce a tumor in the mouse, wherein B7x is stably expressed on the tumor cells using a retroviral expression vector, and   injecting a monclonal antibody to B7x into the mouse to identify an antibody that inhibits tumor growth in vivo.   
     
     
         25 - 26 . (canceled)