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Identification of HLA-A*0201-Presented T Cell Epitopes Derived from the Oncofetal Antigen-Immature Laminin Receptor Protein in Patients with Hematological Malignancies

Sandra Siegel^*, Andreas Wagner^*, Birte Friedrichs^*, Anneke Wendeler^*, Lena Wendel^*, Dieter Kabelitz, Jörg Steinmann, Adel Barsoum, Joseph Coggin, James Rohrer, Peter Dreger, Norbert Schmitz^* and Matthias Zeis^1,*

^* General Hospital St. Georg, Department of Hematology, Hamburg, Germany; Institute of Immunology, University of Kiel, Kiel, Germany; Department of Stem Cell Transplantation, University of Heidelberg, Heidelberg, Germany; and Department of Microbiology and Immunology, University of South Alabama College of Medicine, Mobile, AL 36602

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.

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