Antibodies to MT-SP1 serine protease

Abstract

This invention provides a novel membrane-type serine protease (designated MT-SP1) elevated expression of which is associated with cancer. In one embodiment, this invention provides a method obtaining a prognosis or of detecting or staging a cancer in an organism. The method involves providing a biological sample from the organism and detecting the level of a membrane type serine protease 1 (MT-SP1) in the sample, where an elevated level of the membrane-type serine protease, as compared to the level of the protease in a biological sample from a normal healthy organism indicates the presence or stage of the cancer.

1 - 80 . (canceled) 
     
     
         81 . An isolated antibody that specifically binds to an MT-SP1 proteinase domain that is at least 95% identical to the amino acid sequence from residue 615 to 855 shown in SEQ ID NO. 2. 
     
     
         82 . The antibody of  claim 81 , wherein said antibody is selected from the group consisting of a monoclonal antibody, a polyclonal antibody, a single-chain antibody, and a fragment thereof. 
     
     
         83 . The antibody of  claim 81 , wherein said antibody is a monoclonal antibody. 
     
     
         84 . The antibody of  claim 81 , wherein said antibody specifically binds to an MT-SP1 serine protease domain having the sequence of amino acids 615 through 855 of SEQ ID NO:2. 
     
     
         85 . An isolated cell line that produces the antibody of  claim 81 . 
     
     
         86 . A method for evaluating the severity or outcome of a cancer, said method comprising:
 (a) obtaining a biological sample from a cancer patient having at least a preliminary diagnosis of cancer; and   (b) measuring MT-SP1 in said sample by an immunoassay employing the antibody of  claim 81  and comparing the sample MT-SP1 level to the MT-SP1 level in a control human wherein a sample MT-SP1 level in excess of MT-SP1 levels in the control human indicates a reduced survival expectancy compared to patients with normal MT-SP1 level.   
     
     
         87 . The method of  claim 86 , wherein said patient is diagnosed as having a cancer selected from the group consisting of a prostate cancer, a cancer of the digestive tract, a breast cancer, and a urogenital cancer. 
     
     
         88 . The method of  claim 86 , wherein the level of MT-SP1 is measured by immunohistochemical staining of cells comprising said biological sample. 
     
     
         89 . A method to screen for recurrence of a cancer after removal of a primary tumor, said method comprising:
 (a) obtaining a biological sample from a cancer patient following removal of a primary tumor; and   (b) measuring a level of MT-SP1 in said sample by an immunoassay employing an antibody of  claim 81  and comparing the sample MT-SP1 level to the MT-SP1 level in normal healthy humans wherein a sample MT-SP1 level in excess of MT-SP1 levels in normal healthy humans indicates a possible recurrence of said cancer.   
     
     
         90 . The method of  claim 89 , wherein said method is repeated at a multiplicity of instances after removal of said primary tumor. 
     
     
         91 . A method of monitoring effectiveness of cancer treatment in patients said method comprising:
 (a) obtaining a first biological sample from said patient prior to or following one or more treatments of a cancer;   (b) obtaining a second biological sample from said cancer patient during or after said one or more treatments; and   (c) measuring a level of MT-SP1 in said second biological sample by an immunoassay employing an antibody of  claim 81  and comparing the level of MT-SP1 in said second sample to the level of MT-SP1 in said first sample, wherein a lower level of MT-SP1 in said second sample as compared to the MT-SP1 level in said first sample indicates efficacy of said one or more treatments   
     
     
         92 . The method of  claim 91 , wherein said one or more treatments are selected from the group consisting of chemotherapy, radiation therapy, immunotherapy, antihormone therapy, and surgery. 
     
     
         93 . A method of specifically delivering an effector to a tumor cell expressing MT-SP1, said method comprising:
 (a) providing a chimeric moiety comprising said effector attached to an anti-MT-SP1 antibody of  claim 81 ; and   (b) contacting said tumor with said chimeric moiety whereby said chimeric moiety binds to said tumor cell.   
     
     
         94 . The method of  claim 93 , wherein said tumor cell internalizes at least some of the effector. 
     
     
         95 . The method of  claim 93 , wherein said effector is selected from the group consisting of a cytotoxin, a detectable label, a radionuclide, a drug, a liposome, a ligand, and an antibody. 
     
     
         96 . The method of  claim 93 , wherein said effector molecule is cytotoxic. 
     
     
         97 . A chimeric molecule comprising an effector molecule attached to an anti-MT-SP1 antibody of  claim 81 . 
     
     
         98 . A pharmaceutical composition comprising the chimeric molecule of  claim 97  in a pharmaceutically acceptable excipient. 
     
     
         99 . A method of impairing growth of tumor cells expressing an MT-SP1 protein, said method comprising contacting said tumor with a chimeric molecule comprising;
 an anti-MT-SP1 antibody of  claim 81 ; and   an effector molecule wherein said effector molecule is cytotoxic.   
     
     
         100 . A method of treating a cancer in a patient, said method comprising:
 (a) obtaining a biological sample from a cancer patient having at least a preliminary diagnosis of a cancer,   (b) measuring a level of MT-S P1 by immunoassay with an antibody of  claim 81  in said sample and comparing the sample MT-SP1 level to the MT-SP1 level in normal healthy humans wherein a sample MT-SP1 level in excess of MT-SP1 levels in normal healthy humans indicates a reduced survival expectancy compared to patients with normal MT-SP1 level; and   (c) selecting a patient identified with a MT-SP1 level excess of MT-SP1 levels in normal healthy humans and providing an adjuvant cancer therapy selected from the group consisting of chemotherapy, radiation therapy, reoperation, antihormone therapy, and immunotherapy.   
     
     
         101 . The antibody of  claim 81 , wherein said antibody is a single-chain antibody. 
     
     
         102 . A pharmaceutical composition comprising the antibody of  claim 81  in a pharmaceutically acceptable excipient.