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J Immunol ; 176(11): 6935-44, 2006 Jun 01.
Article in English | MEDLINE | ID: mdl-16709854

ABSTRACT

The oncofetal Ag immature laminin receptor (OFA-iLR) is a potential target molecule for immunotherapeutic studies in several tumor entities, including hematological malignancies. In the present study, we characterize two HLA-A*0201-presented epitopes eliciting strong OFA-iLR peptide-specific human cytotoxic T cell (CTLs) responses in vitro. Both allogeneic HLA-A*0201-matched and autologous CTLs recognized and killed endogenously OFA-iLR-expressing tumor cell lines and primary malignant cells from patients with hemopoietic malignancies in an MHC-restricted fashion but spared nonmalignant hemopoietic cells. Spontaneous OFA-iLR peptide-specific T cell reactivity was detectable in a significant proportion of leukemia patients. Interestingly, in patients with chronic lymphocytic leukemia and multiple myeloma but not in those with acute myeloid leukemia, significant frequencies of OFA peptide-specific CTLs could be detected in an early stage of disease but disappeared in patients with progressive disease. The identification of OFA-iLR-derived peptide epitopes provides a basis for tumor immunological studies and therapeutic vaccination strategies in patients with OFA-iLR-expressing malignancies.


Subject(s)
Antigen Presentation , Antigens, Neoplasm/metabolism , Epitopes, T-Lymphocyte/metabolism , HLA-A Antigens/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Leukemia, Myeloid, Acute/immunology , Multiple Myeloma/immunology , Receptors, Laminin/metabolism , Adult , Aged , Antigens, Neoplasm/biosynthesis , Antigens, Neoplasm/genetics , Antigens, Neoplasm/immunology , Cytotoxicity Tests, Immunologic , Cytotoxicity, Immunologic , Dendritic Cells/immunology , Dendritic Cells/metabolism , Dendritic Cells/pathology , Epitopes, T-Lymphocyte/immunology , Female , HLA-A Antigens/immunology , HLA-A2 Antigen , Humans , K562 Cells , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Multiple Myeloma/metabolism , Multiple Myeloma/pathology , Peptide Fragments/immunology , Peptide Fragments/metabolism , Protein Binding/immunology , Receptors, Laminin/biosynthesis , Receptors, Laminin/genetics , Receptors, Laminin/immunology , Ribosomal Proteins , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/metabolism , T-Lymphocytes, Cytotoxic/pathology , Transfection
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