Soluble mic polypeptides as markers for diagnosis, prognosis and treatment of cancer and autoimmune diseases or conditions

Abstract

The present invention provides prognostic and diagnostic methods for cancer, as well as methods for monitoring or staging cancer. Methods involve assaying for tumor-derived soluble MIC polypeptide—either MICA or MICB or both—in a sample from a subject. Assays can be implemented with a MIC polypeptide binding agent such as a MIC polypeptide antibody or recombinantNKG2D. An ELISA sandwich assay is employed in some embodiments of the invention to identify a soluble MIC polypeptide. In additional embodiments, a sample is assayed for tumor cell-surface bound MIC in addition to assaying for soluble MIC. The invention also provides methods of cancer therapy involving detecting cancer in the subject by assaying for soluble MIC polypeptide and then administering a cancer therapy.

1 .- 73 . (canceled) 
     
     
         74 . A method for treating an autoimmune disease or condition in a subject comprising administering to the subject a composition that binds to an NKG2D receptor and blocks NKG2D ligand binding. 
     
     
         75 . The method of  claim 74 , wherein the composition comprises an antibody that binds NKG2D. 
     
     
         76 . The method of  claim 75 , wherein the antibody is a monoclonal antibody. 
     
     
         77 . The method of  claim 75 , wherein the antibody is 1D11. 
     
     
         78 . The method of  claim 74 , wherein the autoimmune disease or condition is rheumatoid arthritis. 
     
     
         79 . The method of  claim 74 , further comprising administering an immune-suppressive agent. 
     
     
         80 . The method of  claim 79 , wherein the immune-suppressive agent is an NSAID, a steroid, or a cytokine neutralization agent. 
     
     
         81 . A method for abrogating tissue damage facilitated by CD4 + CD28 −  cytotoxic cells expressing NKG2D in a subject comprising contacting the CD4 + CD28 −  cytotoxic cells expressing NKG2D with an anti-NKG2D antibody. 
     
     
         82 . The method of  claim 81 , wherein the anti-NKG2D antibody is a monoclonal antibody. 
     
     
         83 . The method of  claim 82 , wherein the antibody is 1D11. 
     
     
         84 . The method of  claim 81 , wherein the subject is diagnosed with an autoimmune disease or condition. 
     
     
         85 . The method of  claim 84 , wherein the autoimmune disease or condition is rheumatoid arthritis. 
     
     
         86 . A method for treating an autoimmune disease or condition in a subject comprising administering to the subject an antibody that binds soluble MIC, wherein the antibody binds soluble MIC and reduces inflammatory lesions. 
     
     
         87 . The method of  claim 86 , wherein the antibody is a monoclonal antibody. 
     
     
         88 . The method of  claim 87 , wherein the antibody recognizes the α3 domain of MIC. 
     
     
         89 . The method of  claim 87 , wherein the antibody is 6D4 or 6G6. 
     
     
         90 . The method of  claim 87 , wherein the antibody recognizes the distal αα2 domain of MIC. 
     
     
         91 . The method of  claim 90 , wherein the antibody is 2C10 or 3H5. 
     
     
         92 . The method of  claim 86 , wherein the autoimmune disease or condition is rheumatoid arthritis.