Individualized anti-cancer antibodies

Abstract

The present invention relates to a method for producing patient specific anti-cancer 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 customized for the individual patient that can be used for therapeutic and diagnostic purposes. The invention further relates to the process by which the antibodies are made and to their methods of use. The antibodies can be made specifically for one tumor derived from a particular patient and are selected on the basis of their cancer cell cytotoxicity and simultaneous lack of toxicity for non-cancerous cells. The antibodies can be used in aid of staging and diagnosis of a cancer, and can be used to treat tumor metastases. The anti-cancer antibodies can be conjugated to red blood cells obtained from that patient and re-infused for treatment of metastases based upon the recognition that metastatic cancers are usually well vascularized and the delivery of anti-cancer antibodies by red blood cells can have the effect of concentrating the antibodies at the site of the tumor.

1 . A method for treating a patient suffering from a cancerous disease comprising: 
 administering to said patient anti-cancer antibodies or fragments thereof produced in accordance with a method for the production of individually customized anti-cancer antibodies which are useful in treating a cancerous disease, said antibodies including a subset of antibodies or fragments thereof characterized as being cytotoxic against cells of a cancerous tissue, said subset being essentially benign to non-cancerous cells;    wherein one or more antibodies or fragments thereof selected from said subset are placed in admixture with a pharmaceutically acceptable adjuvant and are administered in an amount effective to mediate treatment of said cancerous disease;    said one or more antibodies or fragments thereof being selected from the group consisting of a 1LN-8, 4BD-1, a 4BD-3, a 4BD-6, a 4BD-9, a 4BD-13, a 4BD-18, a 4BD-20, a 4BD-25, a 4BD-26, a 4BD-27, a 4BD-28, a 4BD-32, a 4BD-37, a 4BD-50, a 6BD-1, a 6BD-3, a 6BD-5, a 6BD-11, a 6BD-25, a 7BD-7, a 7BD-12-1, a 7BD-12-2, a 7BD-13, a 7BD-14, a 7BD-19, a 7BD-21, a 7BD-24, a 7BD-29, a 7BD-30, a 7BD-31, a 7BDI-17, a 7BDI-58, a 7BDI-60, a 7BDI-62, a 5LAC2, a 5LAC4, a 5LAC20, a 5LAC23, a H460-1, a H460-4, a H460-5, a H460-10, a H460-14, a H460-16-1, a H460-16-2, a H460-23 and a H460-27 monoclonal antibody or combinations thereof.    
   
   
       2 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 1 , wherein said one or more antibodies or fragments thereof selected from said subset are humanized.  
   
   
       3 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 1  comprising: 
 conjugating said subset of antibodies or fragments thereof with a member selected from the group consisting of toxins, enzymes, radioactive compounds, and hematogenous cells; and    administering conjugated antibodies or fragments thereof to said patient;    wherein said conjugated antibodies are placed in admixture with a pharmaceutically acceptable adjuvant and are administered in an amount effective to mediate treatment of said cancerous disease.    
   
   
       4 . The method of  claim 3 , wherein said one or more antibodies or fragments thereof selected from said subset are humanized.  
   
   
       5 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 1  wherein: 
 the cytotoxicity of said antibodies or fragments thereof is mediated through antibody dependent cellular toxicity.    
   
   
       6 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 1  wherein: 
 the cytotoxicity of said antibodies or fragments thereof is mediated through complement dependent cellular toxicity.    
   
   
       7 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 1  wherein: 
 the cytotoxicity of said antibodies or fragments thereof is mediated through catalyzing of the hydrolysis of cellular chemical bonds.    
   
   
       8 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 1  wherein: 
 the cytotoxicity of said antibodies or fragments thereof is mediated through producing an immune response against putative cancer antigens residing on tumor cells.    
   
   
       9 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 1  wherein: 
 the cytotoxicity of said antibodies or fragments thereof is mediated through targeting of cell membrane proteins to interfere with their function.    
   
   
       10 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 1  wherein: 
 the cytotoxicity of said antibodies or fragments thereof is mediated through production of a conformational change in a cellular protein effective to produce a signal to initiate cell-killing.    
   
   
       11 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 1  wherein: 
 said method of production utilizes a tissue sample containing cancerous and non-cancerous cells obtained from a particular individual.    
   
   
       12 . A method for treating a patient suffering from a cancerous disease comprising: 
 administering to said patient anti-cancer antibodies or fragments thereof produced in accordance with a method for the production of individually customized anti-cancer antibodies which are useful in treating a cancerous disease, said antibodies including a subset of antibodies or fragments thereof characterized as being cytotoxic against cells of a cancerous tissue, said subset being essentially benign to non-cancerous cells;    wherein one or more antibodies or fragments thereof selected from said subset are placed in admixture with a pharmaceutically acceptable adjuvant and are administered in an amount effective to mediate treatment of said cancerous disease;    said one or more antibodies or fragments thereof produced by a hybridoma cell line having an ATCC Accession Number selected from the group consisting of PTA-2693, PTA-2694, PTA-2695, PTA-2696, PTA-2697, PTA-2698, PTA-2699, PTA-2700, PTA-4621, PTA-4622, and PTA-4623 or combinations thereof.    
   
   
       13 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 12 , wherein said one or more antibodies or fragments thereof selected from said subset are humanized.  
   
   
       14 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 12  comprising: 
 conjugating said subset of antibodies or fragments thereof with a member selected from the group consisting of toxins, enzymes, radioactive compounds, and hematogenous cells; and    administering conjugated antibodies or fragments thereof to said patient;    wherein said conjugated antibodies are placed in admixture with a pharmaceutically acceptable adjuvant and are administered in an amount effective to mediate treatment of said cancerous disease.    
   
   
       15 . The method of  claim 14 , wherein said one or more antibodies or fragments thereof selected from said subset are humanized.  
   
   
       16 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 12  wherein: 
 the cytotoxicity of said antibodies or fragments thereof is mediated through antibody dependent cellular toxicity.    
   
   
       17 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 12  wherein: 
 the cytotoxicity of said antibodies or fragments thereof is mediated through complement dependent cellular toxicity.    
   
   
       18 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 12  wherein: 
 the cytotoxicity of said antibodies or fragments thereof is mediated through catalyzing of the hydrolysis of cellular chemical bonds.    
   
   
       19 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 12  wherein: 
 the cytotoxicity of said antibodies or fragments thereof is mediated through producing an immune response against putative cancer antigens residing on tumor cells.    
   
   
       20 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 12  wherein: 
 the cytotoxicity of said antibodies or fragments thereof is mediated through targeting of cell membrane proteins to interfere with their function.    
   
   
       21 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 12  wherein: 
 the cytotoxicity of said antibodies or fragments thereof is mediated through production of a conformational change in a cellular protein effective to produce a signal to initiate cell-killing.    
   
   
       22 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 12  wherein: 
 said method of production utilizes a tissue sample containing cancerous and non-cancerous cells obtained from a particular individual.    
   
   
       23 . Anti-cancer antibodies or fragments thereof selected from the group consisting of a 1LN-1, a 1LN-8, a 1LN-12, a 1LN-14, a 1LN-21, a 1LN-28, a 1LN-29, a 1LN-31, a 1LN-33, a 1LN-34, a 1LN-35, a 2LN-21, a 2LN-28, a 2LN-29, a 2LN-31, a 2LN-33, a 2LN-34, a 2LN-35, a 4BD-1, a 4BD-3, a 4BD-6, a 4BD-9, a 4BD-13, a 4BD-18, a 4BD-20, a 4BD-25, a 4BD-26, a 4BD-27, a 4BD-28, a 4BD-32, a 4BD-37, a 4BD-50, a 6BD-1, a 6BD-3, a 6BD-5, a 6BD-11, a 6BD-25, a 7BD-7, a 7BD-12-1, a 7BD-12-2, a 7BD-13, a 7BD-14, a 7BD-19, a 7BD-21, a 7BD-24, a 7BD-29, a 7BD-30, a 7BD-31, a 7BDI-17, a 7BDI-58, a 7BDI-60, a 7BDI-62, a 5LAC2, a 5LAC4, a 5LAC20, a 5LAC23, a H460-1, a H460-4, a H460-5, a H460-10, a H460-14, a H460-16-1, a H460-16-2, a H460-22-1, a H460-22-2, a H460-23 and a H460-27 monoclonal antibody or combinations thereof.  
   
   
       24 . Anti-cancer antibodies or fragments thereof produced by a hybridoma cell line having an ATCC Accession Number selected from the group consisting of PTA-2693, PTA-2694, PTA-2695, PTA-2696, PTA-2697, PTA-2698, PTA-2699, PTA-2700, PTA-4621, PTA-4622, and PTA-4623.  
   
   
       25 . A binding assay to determine presence of cancerous cells in a tissue sample selected from a tumor originating in colon, prostate, ovarian, lung, breast, or skin tissue comprising: 
 providing a tissue sample from a tumor originating in colon, prostate, ovarian, lung, breast, or skin tissue;    providing an isolated monoclonal antibody or antigen binding fragment thereof encoded by the clone deposited with the ATCC as Accession Number PTA-2700;    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.    
   
   
       26 . A process of isolating or screening for cancerous cells in a tissue sample selected from a tumor originating in colon, prostate, ovarian, lung, breast, or skin tissue comprising: 
 providing a tissue sample from a tumor originating in colon, prostate, ovarian, lung, breast, or skin tissue;    providing an isolated monoclonal antibody or antigen binding fragment thereof encoded by the clone deposited with the ATCC as Accession Number PTA-2700;    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.