title: The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes.
abstract: The epithelial mucin MUC1 is overexpressed on the cell surface of many epithelial malignancies as well as on some B-cell lymphomas and multiple myelomas. Recently, we identified two HLA-A2-restricted T-cell epitopes derived from the MUC1 protein. To further extend the potential application of these peptides, we analyzed the expression of MUC1 on blast cells from patients with acute myelogenous leukemia (AML; n = 43) and several other hematological malignancies including acute lymphoblastic leukemia (n = 24), chronic lymphocytic leukemia (n = 36), hairy cell leukemia (n = 9), follicular lymphoma (n = 7), and multiple myeloma (n = 12). Using reverse transcription-PCR and MUC1-specific monoclonal antibodies, MUC1 expression was found in 67% of AML samples and 92% of myeloma samples. To analyze the presentation of MUC1 peptides by primary AML blasts, we induced MUC1-specific CTLs in vitro using peptide-pulsed dendritic cells from HLA-A2+ healthy donors as antigen-presenting cells. These CTLs efficiently lysed in an antigen-specific and HLA-A2-restricted manner not only target cells pulsed with the antigenic peptide but also tumor cell lines including multiple myeloma cells and primary AML blasts that constitutively expressed both MUC1 and HLA-A2. The specificity of the CTLs was confirmed in a cold target inhibition assay. Our data demonstrate that MUC1-derived peptides are tumor antigens in AML and several other hematological malignancies that could potentially be used for immunotherapeutic approaches.
authors.affiliation: University of Tübingen, Department of Hematology, Oncology, and Immunology, D-72076 Tübingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Brossart
authors.forename: A
authors.initials: A
authors.lastname: Schneider
authors.forename: P
authors.initials: P
authors.lastname: Dill
authors.forename: T
authors.initials: T
authors.lastname: Schammann
authors.forename: F
authors.initials: F
authors.lastname: Grünebach
authors.forename: S
authors.initials: S
authors.lastname: Wirths
authors.forename: L
authors.initials: L
authors.lastname: Kanz
authors.forename: H J
authors.initials: HJ
authors.lastname: Bühring
authors.forename: W
authors.initials: W
authors.lastname: Brugger
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D017951:Antigen Presentation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018396:Mucin-1 / Q000096:biosynthesis / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; C434325:MUC-1 monoclonal antibody; D018396:Mucin-1