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 . (canceled) 
     
     
         2 . (canceled) 
     
     
         3 . An isolated nucleic acid molecule comprising a nucleotide sequence that (i) binds to the nucleotide sequence of  FIG. 2  or  FIG. 4  under the following stringent hybridization conditions: 0.5 M NaHPO4, 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65°, and washing in 0.1×SSC/0.1% SDS at 68° 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 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . An isolated polypeptide comprising the amino acid sequence encoded by the nucleotide sequence of  claim 3 . 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . A recombinant vector comprising the nucleic acid of  claim 3 . 
     
     
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         14 . A recombinant cell comprising the vector of  claim 11 . 
     
     
         15 . (canceled) 
     
     
         16 . A method of producing an antibody with the same immunoreactivity as the 31.1 monclonal antibody, comprising growing a recombinant cell comprising the nucleic acid of  claim 3  such that the encoded light and heavy chain variable regions are expressed by the cell, and recovering the expressed antibody. 
     
     
         17 . 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 according to  claim 6 , and (b) detecting said antigen by detecting the binding of antibody. 
     
     
         18 . An imaging method for detecting a pancreatic carcinoma antigen in a subject, comprising: (a) contacting said pancreatic carcinoma antigen with a labeled antibody according to  claim 6 ; and (b) detecting the labeled antibody wherein detection of said labeled antibody indicates the presence of a pancreatic carcinoma antigen. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . A method of killing cells that express carrying a pancreatic carcinoma associated antigen, comprising delivering to said cells an effective amount of a 31.1 monoclonal antibody. 
     
     
         23 . The method of  claim 22 , wherein said cells are killed in a subject or are cultured cells. 
     
     
         24 . The method of  claim 22 , wherein:
 (a) the light chain of said antibody is encoded by the nucleotide sequence SEQ ID NO: 1, SEQ ID NO: 3, or a humanized variant of SEQ ID NO: 1 or SEQ ID NO: 3; and   (b) the heavy chain of said antibody is encoded by the nucleotide sequence of SEQ ID NO: 4, SEQ ID NO: 6, or a humanized variant of SEQ ID NO: 4 or SEQ ID NO: 6;   
       or wherein said chimerized antibody is expressed by a cell line deposited under ATCC Accession Number CRL-12316 
     
     
         25 . The method of  claim 22 , wherein said antibody is reactive with pancreatic cancer cells. 
     
     
         26 . The method of  claim 22 , wherein said antibody is a recombinant, chimerized, co-specific, or humanized antibody. 
     
     
         27 . The method of  claim 22 , wherein said antibody is selected from the group consisting of a single chain antibody, a F(ab) fragment, and a F(ab) 2  fragment. 
     
     
         28 . The method of  claim 22 , wherein said cells are obtained from a subject or are surgically obtained from a subject. 
     
     
         29 . The method of  claim 22 , wherein the light chain of said antibody is encoded by the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 3, or a humanized variant of SEQ ID NO: 1 or SEQ ID NO: 3, and/or wherein the heavy chain of said antibody is encoded by the nucleotide sequence of SEQ ID NO: 4, SEQ ID NO: 6, or a humanized variant of SEQ ID NO: 4 or SEQ ID NO: 6. 
     
     
         30 . The method of  claim 22 , wherein said antibody or fragment is conjugated to a bioactive agent. 
     
     
         31 . The method of  claim 22 , wherein said method further comprises physical examination or a radiological study to detect the presence of pancreatic cancer in said subject. 
     
     
         32 . The method of claim  36 , wherein said radiological study comprises a chest X-ray, computerized tomography, magnetic resonance imaging, or ultrasound. 
     
     
         33 . The method of  claim 23 , wherein said subject has recurrent or metastatic adenocarcinoma of the pancreas. 
     
     
         34 . The method of  claim 23 , wherein said subject has cancer or is at risk for cancer.