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The Journal of Immunology, 2003, 170: 5391-5397.
Copyright © 2003 by The American Association of Immunologists

Generation of Cytotoxic Responses in Mice and Human Individuals Against Hematological Malignancies Using Survivin-RNA-Transfected Dendritic Cells1

Matthias Zeis2,3,*, Sandra Siegel2,*, Andreas Wagner{dagger}, Marc Schmitz§, Matthias Marget{dagger}, Rita Kühl-Burmeister{ddagger}, Ilse Adamzik{ddagger}, Dieter Kabelitz{dagger}, Peter Dreger*, Norbert Schmitz* and Axel Heiser{dagger}

* General Hospital St. Georg, Hamburg, Germany; Institutes of {dagger} Immunology and {ddagger} Transfusion Medicine, University of Kiel, Kiel, Germany; and § Institute of Immunology, Carl Gustav Carus Technical University, Dresden, Germany

Survivin is a member of the inhibitors of apoptosis family and is overexpressed in many types of human cancers, making it an attractive target for T cell-based immunotherapeutic strategies. Recently, HLA-A2-binding peptides derived from the survivin protein were identified as capable of inducing specific T cell responses in cancer patients. Here we demonstrate that human survivin-specific CTLs generated from PBMC by stimulation with autologous dendritic cells transfected with survivin-RNA were cytotoxic for a range of hemopoietic malignant cell lines and primary tumor cells isolated from patients with acute myeloid leukemia. We also show that vaccination of mice with survivin-RNA-transfected dendritic cells leads to long term resistance to challenge by a survivin-expressing lymphoma, demonstrating the potential of survivin as a tumor rejection Ag. Our data provide evidence for the use of survivin as a target structure for immunotherapeutic strategies against hematological neoplasms.




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