Cytotoxicity Mediation of Cells Evidencing Surface Expression of CD44

Abstract

This invention relates to the staging, diagnosis and treatment of cancerous diseases (both primary tumors and tumor metastases), 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 CDMAB/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. The anti-cancer antibodies can be conjugated to toxins, enzymes, radioactive compounds, cytokines, interferons, target or reporter moieties and hematogenous cells.

1 - 58 . (canceled) 
     
     
         59 . A method of treating human breast, pancreatic, ovarian, prostate or colon cancer in a patient, comprising administering to the patient a pharmaceutically effective amount of a humanized antibody that specifically binds the same epitope or epitopes of human CD44 as an isolated monoclonal antibody produced by the hybridoma cell line H460-16-2 having ATCC Accession No. PTA-4621, comprising:
 a heavy chain variable region comprising the complementarity determining region amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3; and a light chain variable region comprising the complementarity determining region amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6;   or a human CD44 binding fragment thereof.   
     
     
         60 . A method of treating human breast, pancreatic, ovarian, prostate or colon cancer in a patient, comprising administering to the patient a pharmaceutically effective amount of a humanized antibody that specifically binds the same epitope or epitopes of human CD44 as an isolated monoclonal antibody produced by the hybridoma cell line H460-16-2 having ATCC Accession No. PTA-4621, comprising:
 a heavy chain variable region comprising the complementarity determining region amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3; and a light chain variable region comprising the complementarity determining region amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; and variable domain framework regions from the heavy and light chains of a human antibody or human antibody consensus framework;   or a human CD44 binding fragment thereof.   
     
     
         61 . A method of treating human breast, pancreatic, ovarian, prostate or colon cancer in a patient, comprising administering to the patient a pharmaceutically effective amount of a humanized antibody that specifically binds human CD44, wherein the monoclonal antibody comprises a heavy chain variable region amino acid sequence of SEQ ID NO:7; and a light chain variable region amino acid sequence of SEQ ID NO:8; or a human CD44 binding fragment thereof. 
     
     
         62 . The method of  claim 59 , wherein the antibody is conjugated to a cytotoxic moiety. 
     
     
         63 . The method of  claim 59 , wherein the cytotoxic moiety is a radioactive isotope. 
     
     
         64 . The method of  claim 59 , wherein the isolated antibody activates complement. 
     
     
         65 . The method of  claim 59 , wherein the antibody mediates cellular cytotoxicity. 
     
     
         66 . The method of  claim 59 , wherein the method further includes administering to the patient a second therapy to treat the cancer. 
     
     
         67 . The method of  claim 66 , wherein the second therapy is chemotherapy. 
     
     
         68 . The method of  claim 60 , wherein the antibody is conjugated to a cytotoxic moiety. 
     
     
         69 . The method of  claim 60 , wherein the cytotoxic moiety is a radioactive isotope. 
     
     
         70 . The method of  claim 60 , wherein the isolated antibody activates complement. 
     
     
         71 . The method of  claim 60 , wherein the antibody mediates cellular cytotoxicity. 
     
     
         72 . The method of  claim 60 , wherein the method further includes administering to the patient a second therapy to treat the cancer. 
     
     
         73 . The method of  claim 72 , wherein the second therapy is chemotherapy. 
     
     
         74 . The method of  claim 61 , wherein the antibody is conjugated to a cytotoxic moiety. 
     
     
         75 . The method of  claim 61 , wherein the cytotoxic moiety is a radioactive isotope. 
     
     
         76 . The method of  claim 61 , wherein the isolated antibody activates complement. 
     
     
         77 . The method of  claim 61 , wherein the antibody mediates cellular cytotoxicity. 
     
     
         78 . The method of  claim 61 , wherein the method further includes administering to the patient a second therapy to treat the cancer. 
     
     
         79 . The method of  claim 78 , wherein the second therapy is chemotherapy.