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Mammaglobin-A is a tumor-associated antigen in human breast carcinoma
Yoshiyuki Tanaka1, Keith D Amos, Timothy P Fleming
1Washington University School of Medicine, Department of Surgery, St Louis, Mo 63110, USA.
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.