Recognition of breast cancer cells by CD8+ cytotoxic T-cell clones specific for NY-BR-1.
Immunotherapy for breast cancer using cytotoxic T cells (CTL) is hindered by the lack of well-characterized breast cancer antigens that are expressed in most breast tumor cells and recognized by CD8+ CTL. A recently described breast tissue differentiation antigen, NY-BR-1, is expressed in >80% breast tumors and elicits a humoral response in a subset of breast cancer patients. To identify potential NY-BR-1 epitopes that are recognized by CTL, CD8+ T cells were stimulated in vitro with autologous dendritic cells pulsed with NY-BR-1 peptides that were predicted to bind to HLA-A2. In multiple normal female donors and breast cancer patients, specific CD8+ CTL responses were detected by enzyme-linked immunospot assay against several NY-BR-1 peptides after two cycles of stimulation. CD8+ CTL clones against three NY-BR-1 epitopes were isolated and recognized peptide-pulsed target cells with high avidity. T-cell clones specific for one of the NY-BR-1 epitopes (p904) also recognized breast tumor cells expressing NY-BR-1, NY-BR-1(-) cells transfected with a cDNA encoding the NY-BR-1 protein, and autologous dendritic cells pulsed with opsonized NY-BR-1+ breast tumor cells. Taken together, these results show that the p904 epitope derived from NY-BR-1 is efficiently processed and presented endogenously and identify NY-BR-1 as a promising target for T-cell-based immunotherapy for breast cancer.
Wang
Wei
W
Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. wwang@fhcrc.org
Epler
Jennifer
J
Salazar
Lupe G
LG
Riddell
Stanley R
SR
D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
C509866:ANKRD30A protein, human; D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments