Mammaglobin-A is a tumor-associated antigen in human breast carcinoma.
BACKGROUND
Mammaglobin-A is an attractive target for immune-based therapy for patients with breast cancer because of its exclusive expression in breast cancer. In this study, we attempted to identify immunogenic T cell epitopes restricted by human leukocyte antigen (HLA)-A2 in mammaglobin-A protein.


METHODS
To identify HLA-A2-restricted immunogenic epitopes from mammaglobin-A, 7 candidate peptides were synthesized and tested for immunogenicity. Each peptide was tested for binding to HLA-A2 in a HLA-A2 stabilization assay. Furthermore, T lymphocytes from 7 healthy donors and 1 patient with breast cancer received 3 weekly stimulations with autologous peptide-pulsed dendritic cells. Stimulated T cells were tested for specific recognition of peptide and tumor cells by interferon-gamma enzyme-linked immunosorbent assay.


RESULTS
HLA-A2 binding assays showed that all designed peptides could bind to HLA-A2. Two of the 7 peptides (MAM3 and MAM7) successfully induced peptide-specific T cells. However, only MAM3-specific T cells recognized the mammaglobin overexpressing breast cancer cell line, MDA415 transfected with HLA-A2. In contrast, MAM3-specific T cell did not recognize wild type MDA415 or MDA415 transfected with HLA-A24, or the mammaglobin negative, HLA-A2 positive breast cancer cell line, MCF-7.


CONCLUSIONS
Mammaglobin-A-derived peptide, MAM3, can induce mammaglobin-A-specific immunity and could be useful for vaccine strategies for patients with breast cancer.
Tanaka
Yoshiyuki
Y
Washington University School of Medicine, Department of Surgery, St Louis, Mo 63110, USA.
Amos
Keith D
KD
Fleming
Timothy P
TP
Eberlein
Timothy J
TJ
Goedegebuure
Peter S
PS
D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000276:immunology*; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D060785:Mammaglobin A; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014598:Uteroglobin / Q000276:immunology* / Q000378:metabolism
D000951:Antigens, Neoplasm; D000939:Epitopes; D015789:HLA-A2 Antigen; D060785:Mammaglobin A; D009363:Neoplasm Proteins; D010446:Peptide Fragments; C556448:SCGB2A2 protein, human; D014598:Uteroglobin