Recognition of Breast Cancer Cells by CD8+ Cytotoxic T-Cell Clones Specific for NY-BR-1

Abstract

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 À 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. (Cancer Res 2006; 66(13): 6826-33)

Significance, detection and markers of disseminated breast cancer cells

“…In view of its highly restricted expression pattern, ANKRD30A may be considered as a breast M Lacroix: Disseminated breast cancer cells www.endocrinology-journals.org differentiation antigen that could represent a suitable target for immunotherapy , Wang et al 2006. Indeed, it was found in 80% of breast cancer specimens, while tumours of other histological types were ANKRD30A-negative.…”

Immunity to Growth Factor Receptor–Bound Protein 10, a Signal Transduction Molecule, Inhibits the Growth of Breast Cancer in Mice

“…Genetic mutations resulting in the aberrant expression or overexpression of determinants commonly expressed by nonmalignant cells seem to underlie their immunogenic properties. MUC1 (19,20), HER2/neu (21), p53 (22,23), and NY-BR-1 (24)(25)(26) are aberrantly expressed by the malignant cells of breast cancer patients. It is likely that these are only a few representations of an array of tumor antigens that characterize the malignant cell population.…”

The effects of cytokine-induced killer cells for the treatment of patients with solid tumors: a clinical retrospective study

“…Dong et al (Hui et al 2009) analyzed that hepatocellular carcinoma patients received post-operative CIK cells therapy that may prevent recurrence and metastasis. Other preclinical and clinical trials also demonstrated that application of CIK cells had approved beneficial for patients with malignant tumors, such as gastric cancer (Sun et al 2005), renal cell carcinoma (Wang et al 2006) and so on. In our study, 25 patients of all patients were alive, median follow-up was 34.9 months (range, 4-69), and the percentages of CD3 ?…”