Monoclonal antibody for predicting tamoxifen response in breast cancer patients

Abstract

Aspects of the present invention provide a monoclonal antibody specific for BQ323636.1 and its use for prediction of tamoxifen resistance in breast cancer patients.

What is claimed is: 
     
         1 . An antibody or antibody fragment thereof that specifically binds a splice variant of NCOR2, wherein the splice variant is characterized by an exon 11 deletion during mRNA splicing resulting in an early translation stop codon and truncated protein product. 
     
     
         2 . The antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment specifically binds an epitope of NCOR2 consisting of the sequence of SEQ ID NO: 2. 
     
     
         3 . The antibody or antibody fragment of  claim 1 , wherein the antibody is a chimeric, human, or humanized antibody. 
     
     
         4 . The antibody fragment of  claim 1 , wherein the antibody fragment is selected from Fab, Fab′, Fab′-SH, F (ab′) 2, Fv, diabodies, single-chain antibody fragment, and a multispecific antibody comprising multiple different antibody fragments. 
     
     
         5 . The antibody or antibody fragment of  claim 1 , wherein said antibody or antibody fragment is conjugated or covalently bound to a detectable moiety. 
     
     
         6 . An antibody obtained by chimerizing or humanizing an antibody of  claim 1 . 
     
     
         7 . The antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment is a monoclonal antibody. 
     
     
         8 . The antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment has a V H  amino acid sequence of SEQ ID NO: 3. 
     
     
         9 . The antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment has a V L  amino acid sequence of SEQ ID NO: 26. 
     
     
         10 . A kit comprising the antibody or antibody fragment of  claim 1 , the kit optionally further comprising a labeled secondary antibody that specifically recognizes the antibody or antibody fragment of  claim 1 . 
     
     
         11 . A hybridoma or recombinant host cell producing the antibody or antibody fragment of  claim 1 . 
     
     
         12 . A method of determining tamoxifen resistance in a subject with cancer and treating the subject, the method comprising:
 (a) obtaining a tumor sample from the subject;   (b) determining in the sample a level of expression for a splice variant of NCOR2, wherein the splice variant is characterized by an exon 11 deletion during mRNA splicing resulting in an early translation stop codon and truncated protein product, wherein said determining the expression level comprises using the antibody or antibody fragment of  claim 1 ; and   (c) comparing the expression level in (b) to a level of expression in a normal control,   wherein overexpression of the splice variant of NCOR2, with respect to the control, indicates that the cancer is tamoxifen resistant; and   d) treating the subject with chemotherapy if the cancer is tamoxifen resistant.   
     
     
         13 . The method of  claim 12 , wherein the level of expression in the normal control is below an H-Score of 130 and overexpression is a level of expression above an II-Score of 130. 
     
     
         14 . The method of  claim 12 , wherein the subject is a human. 
     
     
         15 . The method of  claim 12 , wherein the cancer is breast cancer. 
     
     
         16 . The method of  claim 15 , wherein the comparing step comprises:
 contacting the sample with the antibody or antibody fragment that specifically recognizes an epitope of NCOR2 consisting of the sequence of SEQ ID NO: 2; and detecting the complex between the antibody or antibody fragment and the splice variant of NCOR2.   
     
     
         17 . The method according to  claim 16 , wherein the splice variant of NCOR2 is contacted with the antibody or antibody fragment that specifically recognizes the splice variant of NCOR2 in an immunoassay selected from the group consisting of radioimmunoassay, western blot assay, immunofluorescent assay, enzyme immunoassay, immunoprecipitation, chemiluminescent assay, immunohistochemical assay, dot blot assay, and slot blot assay. 
     
     
         18 . A method of determining whether a tamoxifen-treated subject is at risk of cancer relapse, or at risk for metastasis, and treating the subject if the subject is at risk of cancer relapse or at risk for metastasis, the method comprising:
 (a) obtaining a tumor sample from the tamoxifen-treated subject;   (b) determining in the sample a level of expression for a splice variant of NCOR2, wherein the splice variant is characterized by an exon 11 deletion during mRNA splicing resulting in an early translation stop codon and truncated protein wherein said determining the level of expression comprises using the antibody or antibody fragment of  claim 1 ; and   (c) comparing the expression level in (b) to a level of expression in a normal control,   wherein overexpression of the splice variant of NCOR2, with respect to the control, indicates that the tamoxifen-treated subject is at risk of cancer relapse or is at risk for metastasis;   and   d) treating the subject with chemotherapy if the cancer is at risk of cancer relapse or at risk for metastasis.   
     
     
         19 . The method of  claim 18 , wherein the subject is a human. 
     
     
         20 . The method of  claim 19 , wherein the cancer is breast cancer.