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Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-01-0198.

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Submitted January 24, 2003
Accepted June 17, 2003

Induction of cytotoxic T-cell responses against the oncofetal antigen-immature laminin receptor for the treatment of hematological malignancies

Sandra Siegel, Andreas Wagner, Dieter Kabelitz, Matthias Marget, Joseph Coggin, Adel Barsoum, James Rohrer, Norbert Schmitz, and Matthias Zeis*

Department of Hematology, General Hospital St. Georg, Hamburg, Germany
Institute of Immunology, University of Kiel, Kiel, Germany
Department of Microbiology and Immunology, University of South Alabama College of Medicine, Mobile, AL, USA

* Corresponding author; email: mzeis47{at}hotmail.com.

The oncofetal-antigen-immature laminin-receptor protein (OFA-iLRP) is a highly conserved protein which is preferentially expressed in fetal tissues and in many types of cancer including hematopoietic malignancies whereas OFA-iLRP is not detectable on normal differentiated adult cells. To investigate whether OFA-iLRP-specific cytotoxic T lymphocytes (CTL) are capable of killing OFA-iLRP-expressing hematological targets, CTL were generated from healthy HLA-A*0201 positive volunteers by incubating T cells with autologous dendritic cells (DC) transfected with OFA-iLRP-RNA. OFA-iLRP-specific CTL lysed HLA-A2+ OFA-iLRP+ tumor cells including several lymphoma and leukemia cell lines, as well as fresh leukemic targets from patients with acute myeloid leukemia (AML) and chronic lymphatic leukemia (CLL) indicating that OFA-iLRP-derived peptides are naturally processed and presented by hematological tumors. Normal OFA-iLRP-negative target cells (CD14+ monocytes, activated B cells, DC, bone marrow cells) were not attacked by OFA-iLRP-specific CTL. Furthermore, in an established murine B-cell lymphoma model (A20) treatment with syngeneic DC transfected with OFA-iLRP-coding RNA resulted in powerful anti-tumor effects in a significant portion of mice. For the first time, these data show that OFA-iLRP can be used as a target for T cell-based immunotherapeutic strategies against hematological malignancies.


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