Identification of HLA-A*0201-presented T cell epitopes derived from the oncofetal antigen-immature laminin receptor protein in patients with hematological malignancies.

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-A0201-presented epitopes eliciting strong OFA-iLR peptide-specific human cytotoxic T cell (CTLs) responses in vitro. Both allogeneic HLA-A0201-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.
Authors	Sandra Siegel, Andreas Wagner, Birte Friedrichs, Anneke Wendeler, Lena Wendel, Dieter Kabelitz, Jörg Steinmann, Adel Barsoum, Joseph Coggin, James Rohrer, Peter Dreger, Norbert Schmitz, Matthias Zeis
Journal	Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 176 Issue 11 Pg. 6935-44 (Jun 01 2006) ISSN: 0022-1767 [Print] United States
PMID	16709854 (Publication Type: Journal Article)
Chemical References	Antigens, Neoplasm Epitopes, T-Lymphocyte HLA-A Antigens HLA-A*02:01 antigen HLA-A2 Antigen Peptide Fragments RPSA protein, human Receptors, Laminin Ribosomal Proteins immature laminin receptor protein, mouse oncofetal antigens
Topics	Adult Aged Antigen Presentation Antigens, Neoplasm (biosynthesis, genetics, immunology, metabolism) Cytotoxicity Tests, Immunologic Cytotoxicity, Immunologic Dendritic Cells (immunology, metabolism, pathology) Epitopes, T-Lymphocyte (immunology, metabolism) Female HLA-A Antigens (immunology, metabolism) HLA-A2 Antigen Humans K562 Cells Leukemia, Lymphocytic, Chronic, B-Cell (immunology, metabolism, pathology) Leukemia, Myeloid, Acute (immunology, metabolism, pathology) Male Middle Aged Multiple Myeloma (immunology, metabolism, pathology) Peptide Fragments (immunology, metabolism) Protein Binding (immunology) Receptors, Laminin (biosynthesis, genetics, immunology, metabolism) Ribosomal Proteins T-Lymphocytes, Cytotoxic (immunology, metabolism, pathology) Transfection

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