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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-08-2554. This Article Full Text (PDF) All Versions of this Article: 2002-08-2554v1 102/2/571    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schmidt, S. M Articles by Brossart, P. Search for Related Content PubMed PubMed Citation Articles by Schmidt, S. M Articles by Brossart, P. Social Bookmarking                   What's this? Submitted August 20, 2002 Accepted January 23, 2003 Survivin is a shared tumor associated antigen expressed in a broad variety of malignancies and recognized by specific cytotoxic T-cells Susanne M Schmidt, Kerstin Schag, Martin R Mueller, Markus M Weck, Silke Appel, Lothar Kanz, Frank Gruenebach, and Peter Brossart* Department of Hematology, Oncology and Immunology, University of Tuebingen, Tuebingen, Germany * Corresponding author; email: peter.brossart{at}med.uni-tuebingen.de. Survivin, a member of the inhibitor of apoptosis protein family, is expressed in almost all types of malignancies making this protein a useful tool for the development of broadly applicable vaccination therapies. We utilized a recently identified HLA-A2 binding peptide and dendritic cells (DC) from healthy donors to induce survivin specific CTL in vitro. These T-cells efficiently lysed target cells pulsed with the cognate peptide. Furthermore, survivin specific CTL recognized HLA-A2 matched tumor cell lines and primary malignant cells from leukemia patients in an antigen specific and HLA-restricted manner as demonstrated using cold target inhibition assays and blocking antibodies. To validate the immunogenicity of survivin we performed the experiments in an autologous setting and used monocyte derived DC as targets. Interestingly, we found that DC upregulate survivin expression upon stimulation with TNF-. However, these mature DC were not recognized by survivin specific CTL while they lysed autologous mature DC pulsed with the antigenic peptide or transfected with whole tumor RNA purified from a survivin expressing cell line. To further analyze the possible use of survivin specific CTL in cancer therapies, we induced survivin specific CTL using PBMNC and DC from a patient with chronic lymphocytic leukemia (CLL). The in vitro generated T-cells efficiently recognized autologous malignant CLL cells while they spared autologous purified non-malignant B-cells or DC. Our results demonstrate that survivin epitopes are presented on a broad variety of malignancies and can be applied in vaccination therapies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. A. Vella, M. Yu, S. R. Fuhrmann, M. El-Amine, D. E. Epperson, and O. J. Finn Healthy individuals have T-cell and antibody responses to the tumor antigen cyclin B1 that when elicited in mice protect from cancer PNAS, August 18, 2009; 106(33): 14010 - 14015. [Abstract] [Full Text] [PDF] T. Nishida, M. Hudecek, A. Kostic, M. Bleakley, E. H. Warren, D. Maloney, R. Storb, and S. R. Riddell Development of Tumor-Reactive T Cells After Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplant for Chronic Lymphocytic Leukemia Clin. 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