Monoclonal antibody therapy for pancreas cancer

Abstract

The present invention relates to the use of binding equivalents of monoclonal antibody 31.1, including chimerized and/or humanized versions thereof, antibody fragments as well as competitively binding and co-specific antibodies and antibody fragments, in the treatment of pancreatic cancer.

1 . An isolated nucleic acid molecule comprising the nucleotide sequences of  FIG. 2  (SEQ ID NOS:1 and 2) or  FIG. 4  (SEQ ID NOS:4 and 5).  
     
     
         2 . An isolated nucleic acid molecule (SEQ ID NOS:1 and 4) comprising a nucleotide sequence that encodes the amino acid sequence shown in  FIG. 2  (SEQ ID NO:3) or  FIG. 4  (SEQ ID NO:6).  
     
     
         3 . An isolated nucleic acid molecule comprising a nucleotide sequence that (i) binds to the nucleotide sequence of  FIG. 2  (SEQ ID NOS:1 and 2) or  FIG. 4  (SEQ ID NOS:4 and 5) under the following stringent hybridization conditions: 0.5 M NaHP0 4 , 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C., and washing in 0.1×SSC/0.1% SDS at 68° C. and (ii) encodes for a light or heavy chain variable region capable of binding with the same immunospecificity as the chimeric 31.1 monoclonal antibody.  
     
     
         4 . An isolated polypeptide comprising the amino acid sequence of  FIG. 2  (SEQ ID NO:3).  
     
     
         5 . An isolated polypeptide comprising the amino acid sequence of  FIG. 4  (SEQ ID NO:6).  
     
     
         6 . An isolated polypeptide comprising the amino acid sequence encoded by a nucleotide sequence that hybridizes to the nucleotide sequence of  claim 1  or  2  under stringent conditions and encodes a functionally equivalent gene product.  
     
     
         7 . A chimeric protein comprising the amino acid sequence of  FIG. 2  (SEQ ID NO:3), or a fragment thereof, fused to an amino acid sequence of a second protein, in which the second protein is not a light chain variable region protein.  
     
     
         8 . A chimeric protein comprising the amino acid sequence of  FIG. 4  (SEQ ID NO:6), or a fragment thereof, fused to an amino acid sequence of a second protein in which the second protein is not a heavy chain variable region protein.  
     
     
         9 . The chimeric protein of  claim 7  or  8  wherein the second protein comprises an immunoglobulin constant region.  
     
     
         10 . The chimeric protein of  claim 9  wherein the immunoglobulin constant region is a human immunoglobulin constant region.  
     
     
         11 . A recombinant vector comprising the nucleic acid of  claim 1 ,  2  or  3 .  
     
     
         12 . A recombinant expression vector comprising the nucleic acid molecule of  claim 1 ,  2  or  3 .  
     
     
         13 . A recombinant cell containing the nucleic acid of  claim 1 ,  2  or  3 .  
     
     
         14 . A recombinant cell comprising the vector of  claim 11  or  12 .  
     
     
         15 . A method of producing a chimeric antibody with the same immunoreactivity as the 31.1 monoclonal antibody, comprising growing a recombinant cell comprising the nucleic acid of  claim 1 ,  2  or  3  such that the encoded light and heavy chain variable regions are expressed by the cell, and recovering the expressed antibody.  
     
     
         16 . An immunoassay method for detecting a pancreatic carcinoma associated antigen capable of binding to monoclonal antibody 31.1, or functional equivalent thereof, -in a sample, comprising: 
 (a) contacting said sample with monoclonal antibody 31.1 or equivalent thereof, and    (b) detecting said antigen by detecting the binding of antibody.    
     
     
         17 . An imaging method for detecting a pancreatic carcinoma antigen in a subject, comprising: 
 (a) contacting a labeled 31.1 antibody, or functional equivalent thereof; and    (b) detecting the labeled antibody wherein detection of said labeled antibody indicates the presence of a pancreatic carcinoma antigen.    
     
     
         18 . A method for diagnosing pancreatic cancer in a subject comprising: 
 (a) removing a specimen from a patient suspected of having a pancreatic carcinoma;    (b) contacting the specimen with a 31.1 monoclonal antibody or functional equivalent thereof;    (c) staining the specimen with an immunohistochemical stain; and    (d) detecting the presence of the antigen-antibody complex wherein the presence of an antigen-antibody complex indicates the presence of pancreatic cancer.    
     
     
         19 . A method of killing cells carrying a pancreatic carcinoma associated antigen, comprising delivering to said cells an effective amount of 31.1 monoclonal antibody, or functional equivalent thereof.