PMID- 12563241 OWN - NLM STAT- MEDLINE DCOM- 20030318 LR - 20220409 IS - 0039-6060 (Print) IS - 0039-6060 (Linking) VI - 133 IP - 1 DP - 2003 Jan TI - Mammaglobin-A is a tumor-associated antigen in human breast carcinoma. PG - 74-80 AB - 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. FAU - Tanaka, Yoshiyuki AU - Tanaka Y AD - Washington University School of Medicine, Department of Surgery, St Louis, Mo 63110, USA. FAU - Amos, Keith D AU - Amos KD FAU - Fleming, Timothy P AU - Fleming TP FAU - Eberlein, Timothy J AU - Eberlein TJ FAU - Goedegebuure, Peter S AU - Goedegebuure PS LA - eng GR - R01 CA68500/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Surgery JT - Surgery JID - 0417347 RN - 0 (Antigens, Neoplasm) RN - 0 (Epitopes) RN - 0 (HLA-A2 Antigen) RN - 0 (Mammaglobin A) RN - 0 (Neoplasm Proteins) RN - 0 (Peptide Fragments) RN - 0 (SCGB2A2 protein, human) RN - 9060-09-7 (Uteroglobin) SB - IM MH - Antigens, Neoplasm/*immunology/metabolism MH - Breast Neoplasms/*diagnosis/*immunology MH - Cells, Cultured MH - Epitopes/immunology/metabolism MH - Female MH - Flow Cytometry MH - HLA-A2 Antigen/metabolism MH - Humans MH - Immunotherapy MH - Mammaglobin A MH - Neoplasm Proteins/*immunology/metabolism MH - Peptide Fragments/immunology/metabolism MH - T-Lymphocytes/immunology MH - Uteroglobin/*immunology/metabolism EDAT- 2003/02/04 04:00 MHDA- 2003/03/19 04:00 CRDT- 2003/02/04 04:00 PHST- 2003/02/04 04:00 [pubmed] PHST- 2003/03/19 04:00 [medline] PHST- 2003/02/04 04:00 [entrez] AID - S003960600221692X [pii] AID - 10.1067/msy.2003.92 [doi] PST - ppublish SO - Surgery. 2003 Jan;133(1):74-80. doi: 10.1067/msy.2003.92.