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.
MeSH terms
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Adult
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Aged
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Antigen Presentation*
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Antigens, Neoplasm / biosynthesis
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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Antigens, Neoplasm / metabolism*
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Cytotoxicity Tests, Immunologic
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Cytotoxicity, Immunologic
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dendritic Cells / pathology
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / metabolism*
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Female
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HLA-A Antigens / immunology
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HLA-A Antigens / metabolism*
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HLA-A2 Antigen
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Humans
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K562 Cells
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Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
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Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
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Leukemia, Lymphocytic, Chronic, B-Cell / pathology
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Leukemia, Myeloid, Acute / immunology*
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Leukemia, Myeloid, Acute / metabolism
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Leukemia, Myeloid, Acute / pathology
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Male
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Middle Aged
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Multiple Myeloma / immunology*
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Multiple Myeloma / metabolism
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Multiple Myeloma / pathology
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Protein Binding / immunology
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Receptors, Laminin / biosynthesis
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Receptors, Laminin / genetics
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Receptors, Laminin / immunology
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Receptors, Laminin / metabolism*
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Ribosomal Proteins
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / metabolism
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T-Lymphocytes, Cytotoxic / pathology
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Transfection
Substances
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Antigens, Neoplasm
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Epitopes, T-Lymphocyte
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HLA-A Antigens
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HLA-A*02:01 antigen
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HLA-A2 Antigen
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Peptide Fragments
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RPSA protein, human
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Receptors, Laminin
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Ribosomal Proteins
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immature laminin receptor protein, mouse
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oncofetal antigens