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Blood, 15 December 2003, Vol. 102, No. 13, pp. 4416-4423.
Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-01-0198.
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IMMUNOBIOLOGY
Induction of cytotoxic T-cell responses against the oncofetal antigen-immature laminin receptor for the treatment of hematologic malignancies
Sandra Siegel,
Andreas Wagner,
Dieter Kabelitz,
Matthias Marget,
Joseph Coggin, Jr,
Adel Barsoum,
James Rohrer,
Norbert Schmitz, and
Matthias Zeis
From the General Hospital St. Georg, Hamburg, Germany; Institute of Immunology, University of Kiel, Germany; and the Department of Microbiology and Immunology, University of South Alabama College of Medicine, Mobile.
The oncofetal antigen immature laminin receptor protein (OFA-iLRP) is a highly conserved protein that is preferentially expressed in fetal tissues and in many types of cancer, including hematopoietic malignancies, whereas OFA-iLRP is not detectable on healthy differentiated adult cells. To investigate whether OFA-iLRP-specific cytotoxic T lymphocytes (CTLs) are capable of killing OFA-iLRP-expressing hematologic targets, CTLs were generated from healthy HLA-A*0201-positive volunteers by incubating T cells with autologous dendritic cells (DCs) transfected with OFA-iLRP RNA. OFA-iLRP-specific CTLs 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 hematologic tumors. Healthy OFA-iLRP-negative target cells (CD14+ monocytes, activated B cells, DCs, bone marrow cells) were not attacked by OFA-iLRP-specific CTLs. Furthermore, in an established murine B-cell lymphoma model (A20), treatment with syngeneic DCs transfected with OFA-iLRP-coding RNA resulted in powerful antitumor 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 hematologic malignancies. (Blood. 2003;102:4416-4423)

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