The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-Lymphocytes

The epithelial mucin MUC1 is overexpressed on the cell surface of many epit helial malignancies as well as on some B-cell lymphomas and multiple myelom as. Recently, we identified two HLA-A2-restricted T-cell epitopes derived f rom the MUC1 protein. To further extend the potential application of these peptides, we analyzed the expression of MUC1 on blast cells from patients w ith acute myelogenous leukemia (AML; n = 43) and several other hematologica l malignancies including acute lymphoblastic leukemia (n = 24), chronic lym phocytic leukemia (n = 36), hairy cell leukemia (n = 9), follicular lymphom a (n = 7), and multiple myeloma (n = 12). Using reverse transcription-PCR a nd MUC1-specific monoclonal antibodies, MUC1 expression was found in 67% of AML samples and 92% of myeloma samples. To analyze the presentation of MUC 1 peptides by primary AML blasts, we induced MUC1-specific CTLs in vitro us ing peptide-pulsed dendritic cells from HLA-A2+ healthy donors as antigen-p resenting cells. These CTLs efficiently lysed in an antigen-specific and HL A-A2-restricted manner not only target cells pulsed with the antigenic pept ide but also tumor cell lines including multiple myeloma cells and primary AML blasts that constitutively expressed both MUC1 and HLA-A2. The specific ity of the CTLs was confirmed in a cold target inhibition assay. Our data d emonstrate that MUC1-derived peptides are tumor antigens in AML and several other hematological malignancies that could potentially be used for immuno therapeutic approaches.