Compositions and methods for treatment

Abstract

The invention concerns compositions and methods for the diagnosis and treatment of neoplastic cell growth and proliferation in mammals, including humans. The invention is based upon the identification of an ADAM8 gene that is amplified in the genome of tumor cells. Such gene amplification is associated with the overexpression of the gene product as compared to normal cells of the same tissue type and contributes to tumorigenesis. Accordingly, the ADAM8 protein encoded by the amplified gene is a useful target for the diagnosis and/or treatment (including prevention) of certain cancers, and acts as a predictor of the prognosis of tumor treatment.

1 - 47 . (canceled) 
     
     
         48 . A method for inhibiting tumor cell growth comprising: exposing tumor cells comprising an amplified gene encoding ADAM8 to an inhibitor of ADAM8, wherein said inhibitor is an antibody or fragment thereof that binds an ADAM8 polypeptide having the sequence of SEQ ID NO: 1; and wherein said exposure inhibits growth of said tumor cells. 
     
     
         49 . A method for inhibiting tumor cell growth comprising: exposing tumor cells that differentially express ADAM8 as compared with normal cells to an inhibitor of ADAM8, wherein said inhibitor is an antibody or fragment thereof that binds an ADAM8 polypeptide having the sequence of SEQ ID NO: 1, and wherein said exposure inhibits growth of said tumor cells. 
     
     
         50 . The method of  claim 48 , wherein said antibody comprises a monoclonal antibody, a humanized antibody, a chimeric antibody, or a fragment thereof. 
     
     
         51 . The method of  claim 49 , wherein said antibody comprises a monoclonal antibody, a humanized antibody, a chimeric antibody, or a fragment thereof. 
     
     
         52 . The method of  claim 48 , further comprising exposing said tumor cells to additional chemotherapeutic agents, radiation, or both. 
     
     
         53 . The method of  claim 49 , further comprising exposing said tumor cells to additional chemotherapeutic agents, radiation, or both. 
     
     
         54 . The method of  claim 52 , wherein said exposure to said inhibitor is concurrent with said exposure to additional chemotherapeutic agents and/or radiation. 
     
     
         55 . The method of  claim 53 , wherein said exposure to said inhibitor is concurrent with said exposure to additional chemotherapeutic agents and/or radiation. 
     
     
         56 . The method of  claim 48 , wherein said tumor cells comprise breast, lung, prostate, or colon tumor cells. 
     
     
         57 . The method of  claim 49 , wherein said tumor cells comprise breast, lung, prostate, or colon tumor cells. 
     
     
         58 . The method of  claim 56 , wherein said tumor cells comprise colon tumor cells. 
     
     
         59 . The method of  claim 57 , wherein said tumor cells comprise colon tumor cells. 
     
     
         60 . A method for inhibiting tumor cell growth comprising:
 exposing colon, lung, prostate, or breast tumor cells that differentially express ADAM8 as compared with normal cells, to an inhibitor of ADAM8, wherein said inhibitor is an antibody or fragment thereof that binds an ADAM8 polypeptide having the amino acid sequence of SEQ ID NO: 1; and wherein said exposure inhibits growth of said tumor cells.   
     
     
         61 . A method for treating inflammatory disease comprising administering an inhibitor of ADAM8. 
     
     
         62 . The method according to  claim 61 , wherein the inflammatory disease comprises chronic inflammatory disease. 
     
     
         63 . The method according to  claim 62 , wherein the chronic inflammatory disease is atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, inflammatory skin disease, sarcoidosis, leukocyte adhesion deficiency, or multiple sclerosis. 
     
     
         64 . The method according to  claim 63 , wherein inflammatory bowel disease comprises Crohn's disease or ulcerative colitis. 
     
     
         65 . The method according to  claim 63 , wherein inflammatory skin disease comprises psoriasis or dermatitis. 
     
     
         66 . The method according to  claim 61 , wherein the inflammatory disease comprises autoimmune disease. 
     
     
         67 . The method according to  claim 66 , wherein the autoimmune disease comprises rheumatoid arthritis, systemic lupus erythematosus, diabetes, Reynaud's syndrome, autoimmune thyroiditis, autoimmune encephalomyelitis, autoimmune hemolytic anemia, or Sjorgen's syndrome. 
     
     
         68 . The method according to  claim 61 , wherein the inflammatory disease comprises immune responses associated with delayed hypersensitivity mediated by cytokines and T-lymphocytes. 
     
     
         69 . The method according to  claim 68 , wherein said immune response associated with delayed hypersensitivity mediated by cytokines and T-lymphocytes comprises tuberculosis, sarcoidosis, polymyositis, granulomatosis, vasculitis, pernicious anemia, chronic obstructive pulmonary disease (COPD), bronchitis, insulinitis, rhinitis, urticaria, or glomerulonephritis. 
     
     
         70 . The method according to  claim 61 , wherein the inflammatory disease comprises a disease involving leukocyte diapedesis. 
     
     
         71 . The method according to  claim 70 , wherein said disease involving leukocyte diapedesis comprises central nervous system (CNS) inflammatory disorder, multiple organ injury syndrome, myasthenia gravis, antigen-antibody complex mediated disease, nephrotic syndrome, malignancies, inflammation related to transplantation, HIV, rhinovirus infection, or pulmonary fibrosis. 
     
     
         72 . The method according to  claim 61 , wherein the inflammatory disease comprises a T cell inflammatory response. 
     
     
         73 . The method according to  claim 72 , wherein the T cell inflammatory response comprises acute respiratory distress syndrome, meningitis, encephalitis, or uveitis. 
     
     
         74 . A method for inhibiting the progression of allergic disease comprising administering an inhibitor of ADAM8. 
     
     
         75 . The method according to  claim 74 , wherein the allergic disease comprises asthma, eczema, or urticaria. 
     
     
         76 . The method according to  claim 61  wherein the inhibitor is a monoclonal antibody. 
     
     
         77 . The method according to  claim 61  wherein the antibody is a bispecific antibody. 
     
     
         78 . The method according to  claim 77  wherein the antibody is selected from the group consisting of Fv, SFv, Fab, Fab′, and F(ab′) 2  fragments. 
     
     
         79 . The method according to  claim 61 , where the inhibitor is a humanized antibody. 
     
     
         80 . The method of  claim 61 , wherein said inhibitor inhibits expression of ADAM8. 
     
     
         81 . The method of  claim 80 , wherein said inhibitor is an antisense oligonucleotide.