| Abstract: |
Cancer immunotherapy depends on the identification of tumor-specific target antigens that are predominantly expressed in cancer cells and not in normal tissues. Here, we report the cloning and the expression analysis of the differentiation antigen NY-BR-1 that we have identified in a previous SEREX (serological analysis of recombinant cDNA expression libraries) screening. The cloning of the full length NY-BR-1 sequence led to the prediction of an open reading frame of 4.2 kb, encoding a protein of 158.9 kDa. NY-BR-1 mRNA expression analysis revealed tissue-specific expression in normal testis and breast tissues, as well as in 70% of breast tumors. We now show that NY-BR-1 is also sporadically expressed in normal prostate and in 32% of prostate tumors. Furthermore, we were able to identify two HLA-A2 restricted NY-BR-1 epitopes (p158-167 and p960-968) that are recognized by CD8+ T cell clones (NW1100-CTL-7 and NW1100-CTL-43, respectively), as determined by ELISPOT analysis and tetramer staining. Cotransfection assays of COS-7 cells also demonstrated that these two peptides are naturally processed and presented on HLA-A2 molecules. The identification of these two naturally processed NY-BR-1-specific CD8+ T cell epitopes opens the perspective for active immunotherapy of HLA-A2 positive patients with NY-BR-1 expressing tumors. © 2005 by Dirk Jäger. |
| Keywords: |
unclassified drug; genetics; nonhuman; cd8+ t lymphocyte; t lymphocyte; cd8-positive t-lymphocytes; animal; animals; cancer immunotherapy; transfection; breast neoplasms; cercopithecus aethiops; cos cells; tumor antigen; prediction; prostatic neoplasms; molecular cloning; cloning, molecular; blood; immunology; cellular immunity; genetic transfection; antigens, neoplasm; tissue distribution; messenger rna; rna, messenger; tumor antigens; nucleotide sequence; breast tumor; prostate tumor; breast carcinoma; epitope; cell strain cos1; cercopithecus; antibody specificity; enzyme linked immunospot assay; epitopes, t-lymphocyte; humoral immunity; serology; testis; antibody formation; antibody production; antigens, differentiation; mrna; differentiation antigen; hla a2 antigen; hla-a2 antigen; immunity, cellular; open reading frame; ny-br-1; hla-a2; t lymphocyte epitope; cancer antigen ny br 1; breast cancer antigen ny br 1, human; breast cancer antigen ny-br-1, human
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