Cancerous disease modifying antibodies

Abstract

The present invention relates to a method for producing patient cancerous disease modifying antibodies using a novel paradigm of screening. By segregating the anti-cancer antibodies using cancer cell cytotoxicity as an end point, the process makes possible the production of anti-cancer antibodies for therapeutic and diagnostic purposes. The antibodies can be used in aid of staging and diagnosis of a cancer, and can be used to treat primary tumors and tumor metastases. The anti-cancer antibodies can be conjugated to toxins, enzymes, radioactive compounds, and hematogenous cells.

What is claimed is:  
     
         1 . A method of treating a human tumor in a mammal, wherein said tumor expresses an antigen which specifically binds to a monoclonal antibody or antigen binding fragment thereof which has the identifying characteristics of a monoclonal antibody encoded by a clone deposited with the ATCC as accession number PTA-4890, comprising administering to said mammal said monoclonal antibody in an amount effective to reduce said mammal's tumor burden.  
     
     
         2 . The method of  claim 1  wherein said antibody is conjugated to a cytotoxic moiety.  
     
     
         3 . The method of  claim 2  wherein said cytotoxic moiety is a radioactive isotope.  
     
     
         4 . The method of  claim 1  wherein said antibody activates complement.  
     
     
         5 . The method of  claim 1  wherein said antibody mediates antibody dependent cellular cytotoxicity.  
     
     
         6 . The method of  claim 1  wherein said antibody is a murine antibody.  
     
     
         7 . The method of  claim 1  wherein said antibody is a humanized antibody  
     
     
         8 . The method of  claim 1  wherein said antibody is a chimerized antibody.  
     
     
         9 . An isolated monoclonal antibody or antigen binding fragments thereof encoded by the clone deposited with the ATCC as accession number PTA-4890.  
     
     
         10 . The isolated antibody or antigen binding fragments of  claim 9 , wherein said isolated antibody or antigen binding fragments thereof is humanized.  
     
     
         11 . The isolated antibody or antigen binding fragments of  claim 9  conjugated with a member selected from the group consisting of cytotoxic moieties, enzymes, radioactive compounds, and hematogenous cells.  
     
     
         12 . The isolated antibody or antigen binding fragments of  claim 9 , wherein said isolated antibody or antigen binding fragments thereof is a chimerized antibody.  
     
     
         13 . The isolated antibody or antigen binding fragments of  claim 9 , wherein said isolated antibody or antigen binding fragments thereof is a murine antibody.  
     
     
         14 . The isolated clone deposited with the ATCC as accession number PTA-4890.  
     
     
         15 . A binding assay to determine presence of cancerous cells in a tissue sample selected from a human tumor comprising: 
 providing a tissue sample from said human tumor;    providing an isolated monoclonal antibody or antigen binding fragment thereof encoded by the clone deposited with the ATCC as accession number PTA-4890;    contacting said isolated monoclonal antibody or antigen binding fragment thereof with said tissue sample; and    determining binding of said isolated monoclonal antibody or antigen binding fragment thereof with said tissue sample;    whereby the presence of said cancerous cells in said tissue sample is indicated.    
     
     
         16 . The binding assay of  claim 15  wherein the human tumor tissue sample is obtained from a tumor originating in a tissue selected from the group consisting of colon, ovarian, lung, and breast tissue.  
     
     
         17 . A process of isolating or screening for cancerous cells in a tissue sample selected from a human tumor comprising: 
 providing a tissue sample from a said human tumor;    providing an isolated monoclonal antibody or antigen binding fragment thereof encoded by the clone deposited with the ATCC as accession number PTA-4890;    contacting said isolated monoclonal antibody or antigen binding fragment thereof with said tissue sample; and    determining binding of said isolated monoclonal antibody or antigen binding fragment thereof with said tissue sample;    whereby said cancerous cells are isolated by said binding and their presence in said tissue sample is confirmed.    
     
     
         18 . The process of  claim 17  wherein the human tumor tissue sample is obtained from a tumor originating in a tissue selected from the group consisting of colon, ovarian, lung, and breast tissue.  
     
     
         19 . A method of treating a human tumor in a mammal, wherein said tumor expresses an antigen which specifically binds to a monoclonal antibody or antigen binding fragment thereof which has the identifying characteristics of a monoclonal antibody encoded by a clone deposited with the ATCC as accession number PTA-4889, comprising administering to said mammal said monoclonal antibody in an amount effective to reduce said mammal's tumor burden.  
     
     
         20 . The method of  claim 19  wherein said antibody is conjugated to a cytotoxic moiety.  
     
     
         21 . The method of  claim 20  wherein said cytotoxic moiety is a radioactive isotope.  
     
     
         22 . The method of  claim 19  wherein said antibody activates complement.  
     
     
         23 . The method of  claim 19  wherein said antibody mediates antibody dependent cellular cytotoxicity.  
     
     
         24 . The method of  claim 19  wherein said antibody is a murine antibody.  
     
     
         25 . The method of  claim 19  wherein said antibody is a humanized antibody  
     
     
         26 . The method of  claim 19  wherein said antibody is a chimerized antibody.  
     
     
         27 . An isolated monoclonal antibody or antigen binding fragments thereof encoded by the clone deposited with the ATCC as accession number PTA-4889.  
     
     
         28 . The isolated antibody or antigen binding fragments of  claim 27 , wherein said isolated antibody or antigen binding fragments thereof is humanized.  
     
     
         29 . The isolated antibody or antigen binding fragments of  claim 27  conjugated with a member selected from the group consisting of cytotoxic moieties, enzymes, radioactive compounds, and hematogenous cells.  
     
     
         30 . The isolated antibody or antigen binding fragments of  claim 27 , wherein said isolated antibody or antigen binding fragments thereof is a chimerized antibody.  
     
     
         31 . The isolated antibody or antigen binding fragments of  claim 27 , wherein said isolated antibody or antigen binding fragments thereof is a murine antibody.  
     
     
         32 . The isolated clone deposited with the ATCC as accession number PTA-4889.  
     
     
         33 . A binding assay to determine presence of cancerous cells in a tissue sample selected from a human tumor comprising: 
 providing a tissue sample from said human tumor;    providing an isolated monoclonal antibody or antigen binding fragment thereof encoded by the clone deposited with the ATCC as accession number PTA-4889;    contacting said isolated monoclonal antibody or antigen binding fragment thereof with said tissue sample; and    determining binding of said isolated monoclonal antibody or antigen binding fragment thereof with said tissue sample;    whereby the presence of said cancerous cells in said tissue sample is indicated.    
     
     
         34 . The binding assay of  claim 33  wherein the human tumor tissue sample is obtained from a tumor originating in a tissue selected from the group consisting of colon, ovarian, lung, and breast tissue.  
     
     
         35 . A process of isolating or screening for cancerous cells in a tissue sample selected from a human tumor comprising: 
 providing a tissue sample from a said human tumor;    providing an isolated monoclonal antibody or antigen binding fragment thereof encoded by the clone deposited with the ATCC as accession number PTA-4889:    contacting said isolated monoclonal antibody or antigen binding fragment thereof with said tissue sample; and    determining binding of said isolated monoclonal antibody or antigen binding fragment thereof with said tissue sample;    whereby said cancerous cells are isolated by said binding and their presence in said tissue sample is confirmed.    
     
     
         36 . The process of  claim 35  wherein the human tumor tissue sample is obtained from a tumor originating in a tissue selected from the group consisting of colon, ovarian, lung, and breast tissue.  
     
     
         37 . A method of treating a human tumor in a mammal, wherein said tumor expresses an antigen which specifically binds to a monoclonal antibody or antigen binding fragment thereof which has the identifying characteristics of a monoclonal antibody encoded by a clone deposited with the ATCC as accession number PTA-5643, comprising administering to said mammal said monoclonal antibody in an amount effective to reduce said mammal's tumor burden.  
     
     
         38 . The method of  claim 37  wherein said antibody is conjugated to a cytotoxic moiety.  
     
     
         39 . The method of  claim 38  wherein said cytotoxic moiety is a radioactive isotope.  
     
     
         40 . The method of  claim 37  wherein said antibody activates complement.  
     
     
         41 . The method of  claim 37  wherein said antibody mediates antibody dependent cellular cytotoxicity.  
     
     
         42 . The method of  claim 37  wherein said antibody is a murine antibody.  
     
     
         43 . The method of  claim 37  wherein said antibody is a humanized antibody  
     
     
         44 . The method of  claim 37  wherein said antibody is a chimerized antibody.  
     
     
         45 . An isolated monoclonal antibody or antigen binding fragments thereof encoded by the clone deposited with the ATCC as accession number PTA-5643.  
     
     
         46 . The isolated antibody or antigen binding fragments of  claim 45 , wherein said isolated antibody or antigen binding fragments thereof is humanized.  
     
     
         47 . The isolated antibody or antigen binding fragments of  claim 45  conjugated with a member selected from the group consisting of cytotoxic moieties, enzymes, radioactive compounds, and hematogenous cells.  
     
     
         48 . The isolated antibody or antigen binding fragments of  claim 45 , wherein said isolated antibody or antigen binding fragments thereof is a chimerized antibody.  
     
     
         49 . The isolated antibody or antigen binding fragments of  claim 45 , wherein said isolated antibody or antigen binding fragments thereof is a murine antibody.  
     
     
         50 . The isolated clone deposited with the ATCC as accession number PTA-5643.  
     
     
         51 . A binding assay to determine presence of cancerous cells in a tissue sample selected from a human tumor comprising: 
 providing a tissue sample from said human tumor;    providing an isolated monoclonal antibody or antigen binding fragment thereof encoded by the clone deposited with the ATCC as accession number PTA-5643;    contacting said isolated monoclonal antibody or antigen binding fragment thereof with said tissue sample; and    determining binding of said isolated monoclonal antibody or antigen binding fragment thereof with said tissue sample;    whereby the presence of said cancerous cells in said tissue sample is indicated.    
     
     
         52 . The binding assay of  claim 51  wherein the human tumor tissue sample is obtained from a tumor originating in a tissue selected from the group consisting of colon, ovarian, lung, and breast tissue.  
     
     
         53 . A process of isolating or screening for cancerous cells in a tissue sample selected from a human tumor comprising: 
 providing a tissue sample from a said human tumor;    providing an isolated monoclonal antibody or antigen binding fragment thereof encoded by the clone deposited with the ATCC as accession number PTA-5643:    contacting said isolated monoclonal antibody or antigen binding fragment thereof with said tissue sample; and    determining binding of said isolated monoclonal antibody or antigen binding fragment thereof with said tissue sample;    whereby said cancerous cells are isolated by said binding and their presence in said tissue sample is confirmed.    
     
     
         54 . The process of  claim 53  wherein the human tumor tissue sample is obtained from a tumor originating in a tissue selected from the group consisting of colon, ovarian, lung, and breast tissue