Cytotoxicity mediation of cells evidencing surface expression of CD44
AssigneeHoffmann-La Roche Inc.
InventorsDavid Young, Helen Findlay, Susan Hahn, Lisa Cechetto, Fortunata McConkey
Life of this patent
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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.
Claims28
An isolated monoclonal antibody encoded by the clone deposited with the IDAC as accession number 280104-06.
The isolated clone deposited with the IDAC as accession number 280104-06.
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 280104-06 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.
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 the clone deposited with the IDAC as accession number 280104-06 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.
A monoclonal antibody or ligand capable of specific binding to human CD44, in which said monoclonal antibody or ligand thereof reacts with the same epitope or epitopes of human CD44 as the isolated monoclonal antibody obtainable from hybridoma cell line H460-16-2 having ATCC Accession No. PTA-4621;
- said monoclonal antibody or ligand being characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target human CD44 antigen.
A monoclonal antibody or ligand capable of specific binding to human CD44, in which said monoclonal antibody or ligand thereof reacts with the same epitope or epitopes of human CD44 as the isolated monoclonal antibody obtainable from hybridoma cell line AR37A335.8 having IDAC Accession No. 280104-06;
- said monoclonal antibody or ligand being characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target human CD44 antigen.
A monoclonal antibody or ligand capable of specific binding to human CD44, in which said monoclonal antibody or ligand thereof reacts with the same epitope or epitopes of human CD44 as the isolated monoclonal antibody obtainable from a hybridoma selected from the group consisting of hybridoma cell line H460-16-2 having ATCC Accession No. PTA-4621 and hybridoma cell line AR37A335.8 having IDAC Accession No. 280104-06;
- said monoclonal antibody or ligand being characterized by an ability to competitively inhibit binding of said isolated monoclonal antibody to its target human CD44 antigen.
A process for treating a human cancerous tumor which expresses human CD44 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 a monoclonal antibody produced by a hybridoma selected from the group consisting of hybridoma cell line H460-16-2 having ATCC Accession No. PTA-4621 and hybridoma cell line AR37A335.8 having IDAC Accession No. 280104-06;
- wherein binding of said epitope or epitopes is effective in reducing tumor burden.
A process for treating a human cancerous tumor which expresses human CD44 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 a monoclonal antibody produced by a hybridoma selected from the group consisting of hybridoma cell line H460-16-2 having ATCC Accession No. PTA-4621 and hybridoma cell line AR37A335.8 having IDAC Accession No. 280104-06;
- in conjunction with at least one chemotherapeutic agent;
- wherein said administration is effective in reducing tumor burden.
A binding assay to determine a presence of cancerous cells which express an epitope or epitopes CD44 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 a monoclonal antibody produced by a hybridoma selected from the group consisting of hybridoma cell line H460-16-2 having ATCC Accession No. PTA-4621 and hybridoma cell line AR37A335.8 having IDAC Accession No. 280104-06;
- 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.
A monoclonal anti-CD44 chimeric antibody or ligand thereof, wherein said monoclonal anti-CD44 chimeric antibody or ligand thereof is characterized by an ability to competitively inhibit binding of CD44 with the isolated monoclonal antibody encoded by the clone deposited with the ATCC as accession number PTA-4621.
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 a monoclonal anti-CD44 chimeric antibody or ligand thereof, wherein said monoclonal anti-CD44 chimeric antibody or ligand thereof is characterized by an ability to competitively inhibit binding of CD44 with the isolated monoclonal antibody encoded by the clone deposited with the ATCC as accession number PTA-4621;
- and
- contacting said monoclonal anti-CD44 chimeric antibody or ligand thereof with said tissue sample.
A method of treating a human tumor susceptible to antibody induced cellular cytotoxicity in a mammal, wherein said human tumor expresses CD44, comprising:
- administering a monoclonal anti-CD44 chimeric antibody or ligand thereof, wherein said monoclonal anti-CD44 chimeric antibody or ligand thereof is characterized by an ability to competitively inhibit binding of CD44 with the isolated monoclonal antibody encoded by the clone deposited with the ATCC as accession number PTA-4621, in an amount effective to induce cellular cytotoxicity and thereby reduce said mammal's tumor burden.
A process for treating a human cancerous tumor which expresses a human CD44 antigen comprising:
- administering to an individual suffering from said human cancer, at least one monoclonal anti-CD44 chimeric antibody or ligand thereof, wherein said monoclonal anti-CD44 chimeric antibody or ligand thereof is characterized by an ability to competitively inhibit binding of CD44 with the isolated monoclonal antibody encoded by the clone deposited with the ATCC as accession number PTA-4621;
- wherein binding of said anti-CD44 chimeric antibody or ligand thereof is effective in reducing tumor burden.
A process for treating a human cancerous tumor which expresses human CD44 antigen comprising:
- administering to an individual suffering from said human cancer, at least one monoclonal anti-CD44 chimeric antibody or ligand thereof, wherein said monoclonal anti-CD44 chimeric antibody or ligand thereof is characterized by an ability to competitively inhibit binding of CD44 with the isolated monoclonal antibody encoded by the clone deposited with the ATCC as accession number PTA-4621:
- wherein said administration of said anti-CD44 chimeric antibody or ligand thereof is effective in reducing tumor burden is effective in reducing tumor burden.
A binding assay to determine a presence of cancerous cells which express human CD44 antigen in a tissue sample selected from a human tumor comprising:
- providing a tissue sample from said human tumor;
- providing at least one monoclonal anti-CD44 chimeric antibody or ligand thereof, wherein said monoclonal anti-CD44 chimeric antibody or ligand thereof is characterized by an ability to competitively inhibit binding of CD44 with the isolated monoclonal antibody encoded by the clone deposited with the ATCC as accession number PTA-4621;
- contacting said at least one anti-CD44 chimeric antibody or ligand thereof with said tissue sample;
- and
- determining binding of said at least one anti-CD44 chimeric antibody or ligand thereof with said tissue sample;
- whereby the presence of said cancerous cells in said tissue sample is indicated.
Dependencies are inferred from the claim text.