Humoral and cellular immune responses against the breast cancer antigen NY-BR-1: definition of two HLA-A2 restricted peptide epitopes.
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.
Jäger
Dirk
D
Medizinische Onkologie, Nationales Centrum für Tumorerkrankungen, Universitätsklinik Heidelberg, Im Neuenheimer Feld 350, D-69120 Heidelberg, Germany. dirk.jaeger@med.uni-heidelberg.de
Karbach
Julia
J
Pauligk
Claudia
C
Seil
Inka
I
Frei
Claudia
C
Chen
Yao-Tseng
YT
Old
Lloyd J
LJ
Knuth
Alexander
A
Jäger
Elke
E
D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000097:blood / Q000276:immunology*; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology*; D012333:RNA, Messenger; D014162:Transfection
C509866:ANKRD30A protein, human; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D012333:RNA, Messenger