Cytotoxicity mediation of cells evidencing surface expression of MCSP

Abstract

This invention relates to the diagnosis and treatment of cancerous diseases, particularly to the mediation of cytotoxicity of tumor cells; and most particularly to the use of cancerous disease modifying antibodies (CDMAB), optionally in combination with one or more chemotherapeutic agents, as a means for initiating the cytotoxic response. The invention further relates to binding assays which utilize the CDMABs of the instant invention.

1 . A method for treating a patient suffering from a cancerous disease comprising:
 administering to said patient an anti-cancer antibody or antigen binding fragment thereof produced in accordance with a method for the production of anti-cancer antibodies which are useful in treating a cancerous disease, said antibody or antigen binding fragment thereof characterized as being cytotoxic against cells of a cancerous tissue, and essentially benign to non-cancerous cells;   wherein said antibody or antigen binding fragment thereof is placed in admixture with a pharmaceutically acceptable adjuvant and is administered in an amount effective to mediate treatment of said cancerous disease;   said antibody being an isolated monoclonal antibody or antigen binding fragment thereof which binds to an antigenic moiety expressed by said cancerous tissue, said antigenic moiety characterized as being bound by an isolated monoclonal antibody or antigen binding fragment thereof produced by the hybridoma deposited with the ATCC as PTA-5643.   
     
     
         2 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 1 , wherein said isolated monoclonal antibody or antigen binding fragment thereof is a humanized or chimeric antibody of the isolated monoclonal antibody produced by the hybridoma deposited with the ATCC as PTA-5643 or an antigen binding fragment thereof. 
     
     
         3 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 1  comprising:
 conjugating said antibody or antigen binding fragment thereof with a member selected from the group consisting of toxins, enzymes, radioactive compounds, and hematogenous cells, thereby forming an antibody conjugate; and   administering said antibody conjugate or conjugated fragments to said patient;   wherein said antibody conjugate or conjugated fragments 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 isolated monoclonal antibody or antigen binding fragment thereof is a humanized or chimeric antibody of the isolated monoclonal antibody produced by the hybridoma deposited with the ATCC as PTA-5643 or an antigen binding fragment thereof. 
     
     
         5 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 1  wherein:
 the cytotoxicity of said antibody or antigen binding fragment 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 antibody or antigen binding fragment 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 antibody or antigen binding fragment 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 antibody or antigen binding fragment 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 antibody or antigen binding fragment 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 antibody or antigen binding fragment 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 an antibody or antigen binding fragment thereof produced in accordance with a method for the production of anti-cancer antibodies which are useful in treating a cancerous disease, said antibody being cytotoxic against cells of a cancerous tissue, and essentially benign to non-cancerous cells;   wherein said antibody is the isolated monoclonal antibody encoded by the clone deposited with the ATCC as PTA-5643 or an antigen binding fragment thereof, and is placed in admixture with a pharmaceutically acceptable adjuvant and is administered in an amount effective to mediate treatment of said cancerous disease.   
     
     
         13 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 12 , wherein said isolated monoclonal antibody or antigen binding fragment thereof is a humanized or chimeric antibody of the isolated monoclonal antibody produced by the hybridoma deposited with the ATCC as PTA-5643 or an antigen binding fragment thereof. 
     
     
         14 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 12  comprising:
 conjugating said antibody or antigen binding fragment thereof with a member selected from the group consisting of toxins, enzymes, radioactive compounds, and hematogenous cells, whereby an antibody conjugate is formed; and   administering said antibody conjugates or antigen binding 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 isolated monoclonal antibody or antigen binding fragment thereof is a humanized or chimeric antibody of the isolated monoclonal antibody produced by the hybridoma deposited with the ATCC as PTA-5643 or an antigen binding fragment thereof. 
     
     
         16 . The method for treating a patient suffering from a cancerous disease in accordance with  claim 12  wherein:
 the cytotoxicity of said antibody or antigen binding fragment 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 antibody or antigen binding fragment 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 antibody or antigen binding fragment 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 antibody or antigen binding fragment 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 antibody or antigen binding fragment 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 antibody or antigen binding fragment 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 . A process for mediating cytotoxicity of a human tumor cell which expresses an MCSP antigenic moiety on the cell surface comprising:
 contacting said tumor cell with an isolated monoclonal antibody or antigen binding fragment thereof, said antibody or antigen binding fragment thereof being an isolated monoclonal antibody or antigen binding fragment thereof which binds to said expressed MCSP antigenic moiety, said antigenic moiety characterized as being bound by the isolated monoclonal antibody produced by the hybridoma deposited with the ATCC as PTA-5643,   whereby cell cytotoxicity occurs as a result of said binding.   
     
     
         24 . The process of  claim 23  wherein said isolated monoclonal antibody or antigen binding fragment thereof is a humanized or chimeric antibody of the isolated monoclonal antibody produced by the hybridoma deposited with the ATCC as PTA-5643 or an antigen binding fragment thereof. 
     
     
         25 . The process of  claim 23  wherein said isolated antibody or antigen binding fragments thereof are conjugated with a member selected from the group consisting of cytotoxic moieties, enzymes, radioactive compounds, and hematogenous cells, whereby an antibody conjugate is formed. 
     
     
         26 . The process of  claim 25  wherein said isolated monoclonal antibody or antigen binding fragment thereof is a humanized or chimeric antibody of the isolated monoclonal antibody produced by the hybridoma deposited with the ATCC as PTA-5643 or an antigen binding fragment thereof. 
     
     
         27 . The process of  claim 23  wherein said isolated antibody or antigen binding fragments thereof are murine. 
     
     
         28 . The process of  claim 23  wherein the human tumor tissue sample is obtained from a tumor originating in a tissue selected from the group consisting of breast, ovarian or melanoma tissue. 
     
     
         29 . A method of extending survival and/or delaying disease progression by treating a human tumor in a mammal, wherein said tumor expresses an antigen which specifically binds to an isolated monoclonal antibody or antigen binding fragment thereof produced by the hybridoma 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, whereby disease progression is delayed and/or survival is extended. 
     
     
         30 . The method of  claim 29  wherein said antibody is conjugated to a cytotoxic moiety. 
     
     
         31 . The method of  claim 30  wherein said cytotoxic moiety is a radioactive isotope. 
     
     
         32 . The method of  claim 29  wherein said antibody activates complement. 
     
     
         33 . The method of  claim 29  wherein said antibody mediates antibody dependent cellular cytotoxicity. 
     
     
         34 . The method of  claim 29  wherein said antibody is a murine antibody. 
     
     
         35 . The method of  claim 29  wherein said isolated monoclonal antibody or antigen binding fragment thereof is a humanized antibody of the isolated monoclonal antibody produced by the hybridoma deposited with the ATCC as PTA-5643 or an antigen binding fragment thereof. 
     
     
         36 . The method of  claim 29  wherein said isolated monoclonal antibody or antigen binding fragment thereof is a chimeric antibody of the isolated monoclonal antibody produced by the hybridoma deposited with the ATCC as PTA-5643 or an antigen binding fragment thereof.