Cytotoxicity mediation of cells evidencing surface expression of CD63

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 CDMAB of the instant invention.

1 . An isolated monoclonal antibody encoded by the clone deposited with the IDAC as accession number 141205-01. 
     
     
         2 . The antibody of  claim 1 , which is humanized. 
     
     
         3 . The antibody of  claim 1 , which is chimerized. 
     
     
         4 . The isolated clone deposited with the IDAC as accession number 141205-01. 
     
     
         5 . A method for initiating antibody induced cellular cytotoxicity of cancerous cells in a tissue sample selected from a human tumor comprising:
 providing a tissue sample from said human tumor;   providing the isolated monoclonal antibody encoded by a clone deposited with the IDAC as accession number 141205-01 or a cellular cytotoxicity inducing ligand thereof, which ligand is characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target antigen; and   contacting said isolated monoclonal antibody or cellular cytotoxicity inducing ligand thereof with said tissue sample;   wherein binding of said isolated monoclonal antibody or cellular cytotoxicity inducing ligand thereof with said tissue sample induces cellular cytotoxicity.   
     
     
         6 . A ligand of the isolated monoclonal antibody of  claim 1 . 
     
     
         7 . A ligand of the humanized antibody of  claim 2 . 
     
     
         8 . A ligand of the chimerized antibody of  claim 3 . 
     
     
         9 . The isolated antibody or ligand of any one of  claims 1 ,  2 ,  3 ,  6 ,  7  or  8  conjugated with a member selected from the group consisting of cytotoxic moieties, enzymes, radioactive compounds, and hematogenous cells. 
     
     
         10 . A method of treating a human tumor susceptible to antibody induced cellular cytotoxicity in a mammal, wherein said human tumor expresses an antigen which specifically binds to the isolated monoclonal antibody encoded by a clone deposited with the IDAC as accession number 141205-01 or a cellular cytotoxicity inducing ligand thereof, which ligand is characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target antigen, comprising administering to said mammal said monoclonal antibody or said cellular cytotoxicity inducing ligand thereof in an amount effective to induce cellular cytotoxicity and thereby reduce said mammal's tumor burden. 
     
     
         11 . The method of  claim 10  wherein said monoclonal antibody or ligand is conjugated to a cytotoxic moiety. 
     
     
         12 . The method of  claim 11  wherein said cytotoxic moiety is a radioactive isotope. 
     
     
         13 . The method of  claim 10  wherein said monoclonal antibody or ligand activates complement. 
     
     
         14 . The method of  claim 10  wherein said monoclonal antibody or ligand mediates antibody dependent cellular cytotoxicity. 
     
     
         15 . The method of  claim 10  wherein said monoclonal antibody is humanized. 
     
     
         16 . The method of  claim 10  wherein said monoclonal antibody is chimerized. 
     
     
         17 . An isolated monoclonal antibody encoded by the clone deposited with the IDAC as accession number 141205-06. 
     
     
         18 . The antibody of  claim 17 , which is humanized. 
     
     
         19 . The antibody of  claim 17 , which is chimerized. 
     
     
         20 . The isolated clone deposited with the IDAC as accession number 141205-06. 
     
     
         21 . A method for initiating antibody induced cellular cytotoxicity of cancerous cells in a tissue sample selected from a human tumor comprising:
 providing a tissue sample from said human tumor;   providing the isolated monoclonal antibody encoded by a clone deposited with the IDAC as accession number 141205-06 or a cellular cytotoxicity inducing ligand thereof, which ligand is characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target antigen; and   contacting said isolated monoclonal antibody or cellular cytotoxicity inducing ligand thereof with said tissue sample;   wherein binding of said isolated monoclonal antibody or cellular cytotoxicity inducing ligand thereof with said tissue sample induces cellular cytotoxicity.   
     
     
         22 . A ligand of the isolated monoclonal antibody of  claim 17 . 
     
     
         23 . A ligand of the humanized antibody of  claim 18 . 
     
     
         24 . A ligand of the chimerized antibody of  claim 19 . 
     
     
         25 . The isolated antibody or antigen ligand of any one of  claims 17 ,  18 ,  19 ,  22 ,  23  or  24  conjugated with a member selected from the group consisting of cytotoxic moieties, enzymes, radioactive compounds, and hematogenous cells. 
     
     
         26 . A method of treating a human tumor susceptible to antibody induced cellular cytotoxicity in a mammal, wherein said human tumor expresses an antigen which specifically binds to the isolated monoclonal antibody encoded by a clone deposited with the IDAC as accession number 141205-06 or a cellular cytotoxicity inducing ligand thereof, which ligand is characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target antigen, comprising administering to said mammal said monoclonal antibody or said cellular cytotoxicity inducing ligand thereof in an amount effective to induce cellular cytotoxicity and thereby reduce said mammal's tumor burden. 
     
     
         27 . The method of  claim 26  wherein said monoclonal antibody or ligand is conjugated to a cytotoxic moiety. 
     
     
         28 . The method of  claim 27  wherein said cytotoxic moiety is a radioactive isotope. 
     
     
         29 . The method of  claim 26  wherein said monoclonal antibody or ligand activates complement. 
     
     
         30 . The method of  claim 26  wherein said monoclonal antibody or ligand mediates antibody dependent cellular cytotoxicity. 
     
     
         31 . The method of  claim 26  wherein said monoclonal antibody is humanized. 
     
     
         32 . The method of  claim 26  wherein said monoclonal antibody is chimerized. 
     
     
         33 . An isolated monoclonal antibody encoded by the clone deposited with the ATCC as accession number PTA-4623. 
     
     
         34 . The antibody of  claim 33 , which is humanized. 
     
     
         35 . The antibody of  claim 33 , which is chimerized. 
     
     
         36 . The isolated clone deposited with the ATCC as accession number PTA-4623. 
     
     
         37 . A method for initiating antibody induced cellular cytotoxicity of cancerous cells in a tissue sample selected from a human tumor comprising:
 providing a tissue sample from said human tumor;   providing the isolated monoclonal antibody encoded by a clone deposited with the ATCC as accession number PTA-4623 or a cellular cytotoxicity inducing ligand thereof, which ligand is characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target antigen; and   contacting said isolated monoclonal antibody or cellular cytotoxicity inducing ligand thereof with said tissue sample;   wherein binding of said isolated monoclonal antibody or cellular cytotoxicity inducing ligand thereof with said tissue sample induces cellular cytotoxicity.   
     
     
         38 . A ligand of the isolated monoclonal antibody of  claim 33 . 
     
     
         39 . A ligand of the humanized antibody of  claim 34 . 
     
     
         40 . A ligand of the chimerized antibody of  claim 35 . 
     
     
         41 . The isolated antibody or ligand of any one of  claims 33 ,  34 ,  35 ,  38 ,  39  or  40  conjugated with a member selected from the group consisting of cytotoxic moieties, enzymes, radioactive compounds, and hematogenous cells. 
     
     
         42 . A method of treating a human tumor susceptible to antibody induced cellular cytotoxicity in a mammal, wherein said human tumor expresses an antigen which specifically binds to the isolated monoclonal antibody encoded by a clone deposited with the ATCC as accession number PTA-4623 or a cellular cytotoxicity inducing ligand thereof, which ligand is characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target antigen, comprising administering to said mammal said monoclonal antibody or said cellular cytotoxicity inducing ligand thereof in an amount effective to induce cellular cytotoxicity and thereby reduce said mammal's tumor burden. 
     
     
         43 . The method of  claim 42  wherein said monoclonal antibody or ligand is conjugated to a cytotoxic moiety. 
     
     
         44 . The method of  claim 43  wherein said cytotoxic moiety is a radioactive isotope. 
     
     
         45 . The method of  claim 42  wherein said monoclonal antibody or ligand activates complement. 
     
     
         46 . The method of  claim 42  wherein said monoclonal antibody or ligand mediates antibody dependent cellular cytotoxicity. 
     
     
         47 . The method of  claim 42  wherein said monoclonal antibody is humanized. 
     
     
         48 . The method of  claim 42  wherein said monoclonal antibody is chimerized. 
     
     
         49 . A monoclonal antibody capable of specific binding to human CD63, in which the monoclonal antibody reacts with the same epitope or epitopes of human CD63 as the monoclonal antibody obtainable from a hybridoma cell line H460-22-1 having ATCC Accession No. PTA-4622. 
     
     
         50 . A monoclonal antibody or ligand capable of specific binding to human CD63, in which said monoclonal antibody or ligand thereof reacts with the same epitope or epitopes of human CD63 as the isolated monoclonal antibody obtainable from hybridoma cell line 1A245.6 having ATCC Accession No. PTA-4889; said monoclonal antibody or ligand being characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target human CD63 antigen. 
     
     
         51 . A monoclonal antibody or ligand capable of specific binding to human CD63, in which said monoclonal antibody or ligand thereof reacts with the same epitope or epitopes of human CD63 as the isolated monoclonal antibody obtainable from hybridoma cell line 7BD-33-11A having ATCC Accession No. PTA-4890; said monoclonal antibody or ligand being characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target human CD63 antigen. 
     
     
         52 . A monoclonal antibody or ligand capable of specific binding to human CD63, in which said monoclonal antibody or ligand thereof reacts with the same epitope or epitopes of human CD63 as the isolated monoclonal antibody obtainable from hybridoma cell line 7BDI-60 having ATCC Accession No. PTA-4623; said monoclonal antibody or ligand being characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target human CD63 antigen. 
     
     
         53 . A monoclonal antibody or ligand capable of specific binding to human CD63, in which said monoclonal antibody or ligand thereof reacts with the same epitope or epitopes of human CD63 as the isolated monoclonal antibody obtainable from hybridoma cell line 7BDI-58 having IDAC Accession No. 141205-01; said monoclonal antibody or ligand being characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target human CD63 antigen. 
     
     
         54 . A monoclonal antibody or ligand capable of specific binding to human CD63, in which said monoclonal antibody or ligand thereof reacts with the same epitope or epitopes of human CD63 as the isolated monoclonal antibody obtainable from hybridoma cell line AR51A994.1 having IDAC Accession No. 141205-06; said monoclonal antibody or ligand being characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target human CD63 antigen. 
     
     
         55 . A monoclonal antibody or ligand that recognizes the same epitope or epitopes as those recognized by a monoclonal antibody produced by a hybridoma selected from the group consisting of hybridoma cell line H460-22-1 having ATCC Accession No. PTA-4622, hybridoma cell line 1A245.6 having ATCC Accession No. PTA-4889, hybridoma cell line 7BD-33-11A having ATCC Accession No. PTA-4890, hybridoma cell line 7BDI-60 having ATCC Accession No. PTA-4623, hybridoma cell line 7BDI-58 having IDAC Accession No. 141205-01 and hybridoma cell line AR51A994.1 having IDAC Accession No. 141205-06. 
     
     
         56 . A process for treating a human cancerous tumor which expresses human CD63 antigen comprising:
 administering to an individual suffering from said human cancer, at least one monoclonal antibody or ligand that recognizes the same epitope or epitopes as those recognized by the isolated monoclonal antibody produced by a hybridoma selected from the group consisting of hybridoma cell line H460-22-1 having ATCC Accession No. PTA-4622, hybridoma cell line 1A245.6 having ATCC Accession No. PTA-4889, hybridoma cell line 7BD-33-11A having ATCC Accession No. PTA-4890, hybridoma cell line 7BDI-60 having ATCC Accession No. PTA-4623, hybridoma cell line 7BDI-58 having IDAC Accession No. 141205-01 and hybridoma cell line AR51A994.1 having IDAC Accession No. 141205-06;   wherein binding of said epitope or epitopes is effective in reducing tumor burden.   
     
     
         57 . A process for treating a human cancerous tumor which expresses human CD63 antigen comprising:
 administering to an individual suffering from said human cancer, at least one monoclonal antibody or ligand that recognizes the same epitope or epitopes as those recognized by the isolated monoclonal antibody produced by a hybridoma selected from the group consisting of hybridoma cell line H460-22-1 having ATCC Accession No. PTA-4622, hybridoma cell line 1A245.6 having ATCC Accession No. PTA-4889, hybridoma cell line 7BD-33-11A having ATCC Accession No. PTA-4890, hybridoma cell line 7BDI-60 having ATCC Accession No. PTA-4623, hybridoma cell line 7BDI-58 having IDAC Accession No. 141205-01 and hybridoma cell line AR51A994.1 having IDAC Accession No. 141205-06; in conjunction with at least one chemotherapeutic agent;   wherein said administration is effective in reducing tumor burden.   
     
     
         58 . A binding assay to determine a presence of cells which express an epitope or epitopes of CD63 in a primate tissue sample comprising:
 providing a tissue sample from said primate;   providing at least one monoclonal antibody or ligand that recognizes the same epitope or epitopes as those recognized by the isolated monoclonal antibody produced by a hybridoma selected from the group consisting of hybridoma cell line H460-22-1 having ATCC Accession No. PTA-4622, hybridoma cell line 1A245.6 having ATCC Accession No. PTA-4889, hybridoma cell line 7BD-33-11A having ATCC Accession No. PTA-4890, hybridoma cell line 7BDI-60 having ATCC Accession No. PTA-4623, hybridoma cell line 7BDI-58 having IDAC Accession No. 141205-01 and hybridoma cell line AR51A994.1 having IDAC Accession No. 141205-06;   contacting said at least one monoclonal antibody or ligand thereof with said primate tissue sample; and   determining binding of said at least one monoclonal antibody or ligand thereof with said primate tissue sample;   whereby the presence of said cells in said primate tissue sample is indicated.   
     
     
         59 . A binding assay to determine a presence of cancerous cells which express an epitope or epitopes of CD63 in a tissue sample selected from a human tumor comprising:
 providing a tissue sample from said human tumor;   providing at least one monoclonal antibody or ligand that recognizes the same epitope or epitopes as those recognized by the isolated monoclonal antibody produced by a hybridoma selected from the group consisting of hybridoma cell line H460-22-1 having ATCC Accession No. PTA-4622, hybridoma cell line 1A245.6 having ATCC Accession No. PTA-4889, hybridoma cell line 7BD-33-11A having ATCC Accession No. PTA-4890, hybridoma cell line 7BDI-60 having ATCC Accession No. PTA-4623, hybridoma cell line 7BDI-58 having IDAC Accession No. 141205-01 and hybridoma cell line AR51A994.1 having IDAC Accession No. 141205-06;   contacting said at least one monoclonal antibody or ligand thereof with said tissue sample; and   determining binding of said at least one monoclonal antibody or ligand thereof with said tissue sample;   whereby the presence of said cancerous cells in said tissue sample is indicated.