Recognition of Breast Cancer Cells by CD8+ Cytotoxic T-Cell Clones Specific for NY-BR-1
Open Access
- 1 July 2006
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 66 (13), 6826-6833
- https://doi.org/10.1158/0008-5472.can-05-3529
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− 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)Keywords
This publication has 28 references indexed in Scilit:
- Recruitment of latent pools of high-avidity CD8+ T cells to the antitumor immune responseThe Journal of Experimental Medicine, 2005
- Adoptive-cell-transfer therapy for the treatment of patients with cancerNature Reviews Cancer, 2003
- Tumor Regression and Autoimmunity after Reversal of a Functionally Tolerant State of Self-reactive CD8+ T CellsThe Journal of Experimental Medicine, 2003
- Three or more routes for leukocyte migration into the central nervous systemNature Reviews Immunology, 2003
- Opening AddressOphthalmologica, 2003
- Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor LymphocytesScience, 2002
- Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarraysOncogene, 2002
- Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patientsJCI Insight, 2001
- Identification of an immunodominant peptide of HER-2/neu protooncogene recognized by ovarian tumor-specific cytotoxic T lymphocyte lines.The Journal of Experimental Medicine, 1995
- Tumor Antigens Recognized by T LymphocytesAnnual Review of Immunology, 1994