COMPOSITIONS AND METHODS OF USE FOR DETERMINATION OF HE4a

Abstract

The invention includes the use of the HE/HE4a markers to assess ovarian cancer in a subject. Included also are compositions and methods of using HE/HE4a marker for diagnosis, grading and staging of ovarian cancers, determining prognosis and treatment effectiveness of a subject who has been diagnosed with ovarian cancer.

1 . An antibody that specifically binds an epitope within the amino acid sequence of the N-WFDC domain of an HE4a polypeptide as set forth in SEQ ID NO.: 17, wherein the epitope is an epitope recognized by the monoclonal antibody produced by the hybridoma cell line 12A2, deposited with the ECACC as Patent Deposit No. 10091401, and wherein the antibody is optionally labeled with a detectable marker. 
     
     
         2 . The antibody of  claim 1 , wherein the antibody is a polyclonal antibody, a monoclonal antibody, a bispecific antibody, a chimeric antibody, a humanized antibody, or an antigen-binding fragment of the polyclonal, monoclonal, bispecific, chimeric or humanized antibody. 
     
     
         3 . The antibody of  claim 1 , wherein the antibody is a monoclonal antibody produced by the hybridoma cell line 12A2, deposited with the ECACC as Patent Deposit No. 10091401. 
     
     
         4 . The antibody of  claim 1 , wherein the antibody is detectably labeled. 
     
     
         5 . The antibody of  claim 1 , wherein the epitope is a linear epitope. 
     
     
         6 . The antibody of  claim 1 , wherein the epitope is a conformational dependent epitope. 
     
     
         7 . A kit comprising the antibody of  claim 1 . 
     
     
         8 . The kit of  claim 7 , further comprising an antibody that specifically binds to the C-WFDC domain of an HE4a polypeptide. 
     
     
         9 . The kit of  claim 7 , further comprising a second antibody that specifically binds an epitope in the N-WFDC domain of an HE4a polypeptide as set forth in SEQ ID NO: 17, wherein the second antibody recognizes an epitope distinct from the epitope recognized by the monoclonal antibody produced by the hybridoma cell line 12A2, deposited with the ECACC as Patent Deposit No. 10091401. 
     
     
         10 . A method of screening for the presence of an ovarian cancer in a subject, the method comprising:
 (a) contacting a biological sample from the subject with at least one monoclonal antibody that specifically binds an epitope within the amino acid sequence of the N-WFDC domain of an HE4a polypeptide as set forth in SEQ ID NO: 17, wherein the epitope is an epitope recognized by the monoclonal antibody produced by the hybridoma cell line 12A2, deposited with the ECACC as Patent Deposit No. 10091401, and wherein the antibody is optionally labeled with a detectable marker, under conditions and for a time sufficient to form an antigen-antibody complex; and   (b) detecting the antigen-antibody complex, wherein an elevated level of the antigen-antibody complex in the biological sample relative to a reference value is an indication that the subject has an increased likelihood of having ovarian cancer.   
     
     
         11 . The method of  claim 10 , further comprising contacting the biological sample from the subject with an antibody that specifically binds the C-WFDC domain of the HE4a polypeptide. 
     
     
         12 . The method of  claim 10 , wherein the epitope is a linear epitope. 
     
     
         13 . The method of  claim 10 , wherein the epitope is a conformational dependent epitope. 
     
     
         14 . The method of  claim 10 , wherein the at least one antibody that specifically binds an epitope within the amino acid sequence of the N-WFDC domain of an HE4a polypeptide as set forth in SEQ ID NO: 17 antibody is a monoclonal antibody produced by the hybridoma cell line 12A2, deposited with the ECACC as Patent Deposit No. 10091401. 
     
     
         15 . The method of  claim 10 , wherein the antibody that specifically binds the C-WFDC domain of the HE4a polypeptide is detectably labeled. 
     
     
         16 . The method of  claim 10 , wherein the detectable label is an enzyme, dye, radionuclide, luminescent group, fluorescent group or biotin. 
     
     
         17 . The method of  claim 10 , wherein the biological sample comprises blood, serum, serosal fluid, plasma, lymph, urine, cerebrospinal fluid, saliva, a mucosal secretion, a vaginal secretion, conditioned culture medium, or a lavage fluid. 
     
     
         18 . The method of  claim 10 , wherein at least one antibody is immobilized on a solid support. 
     
     
         19 . The method of  claim 10 , wherein the method is configured as a two-antibody sandwich assay. 
     
     
         20 . The method of  claim 10 , wherein the subject is undergoing treatment for ovarian cancer and the method is carried out to monitor the course of the disease.