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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2591-2599. Prepublished online as a Blood First Edition Paper on July 1, 2004; DOI 10.1182/blood-2004-02-0459. This Article Full Text (PDF) All Versions of this Article: 2004-02-0459v1 104/8/2591    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 Doerrschuck, A. Articles by Herr, W. Search for Related Content PubMed PubMed Citation Articles by Doerrschuck, A. Articles by Herr, W. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 9, 2004 Accepted June 14, 2004 CD8+ cytotoxic T lymphocytes isolated from allogeneic healthy donors recognize HLA-class Ia/Ib-associated renal carcinoma antigens with ubiquitous or restricted tissue expression Andreas Doerrschuck, Andrea Schmidt, Elke Schnuerer, Matthias Glueckmann, Christian Albrecht, Catherine Woelfel, Volker Lennerz, Alexander Lifke, Carmela Di Natale, Elena Ranieri, Loreto Gesualdo, Christoph Huber, Michael Karas, Thomas Woelfel, and Wolfgang Herr* Department of Medicine III, Johannes Gutenberg-University of Mainz, Mainz, Germany Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe-University of Frankfurt, Frankfurt, Germany Applied Biosystems, Darmstadt, Germany Department of Nephrology, University of Bari, Bari, Italy * Corresponding author; email: w.herr{at}3-med.klinik.uni-mainz.de. Allogeneic hematopoietic stem-cell transplantation can induce considerable tumor remissions in metastatic renal-cell carcinoma (RCC) patients. The precise effector mechanisms mediating these graft-versus-tumor reactions are unknown. We studied RCC-directed CD8+ T-cell responses in blood lymphocytes of healthy individuals matched with established RCC-cell lines for HLA-class I. In 21 of 22 allogeneic mixed lymphocyte/tumor-cell cultures (MLTC), RCC-reactive cytotoxic T-lymphocytes (CTL) were readily obtained. From MLTC, 121 CD8+ CTL clones with memory phenotype were isolated. Their anti-RCC-reactivity was restricted by multiple classical HLA-Ia molecules, in particular by HLA-A2, -A3, -B7, -B44, -Cw7, and by a nonclassical HLA-Ib determinant. Extensive cross-reactivity analyses on a broad target panel identified CTL recognizing antigens with expression restricted to renal tissue or to renal and colon tumors. Other CTL were directed against antigens with broader tissue distribution being expressed in various epithelial and nonepithelial tumors or, additionally, in hematopoietic cells. With microcapillary LC and MALDI-TOF/TOF mass spectrometry, we identified the HLA-A*0301-associated nonpolymorphic peptide KLPNSVLGR encoded by the ubiquitously expressed Eps15 homology-domain containing-2 gene as a CTL target. Defining human RCC antigens recognized by alloreactive CTL may allow to improve the specificity and efficiency of allogeneic cell therapy (e.g. specific donor-lymphocyte infusions or vaccination) in metastatic RCC patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Conrad, M. Remberger, K. Cederlund, O. Ringden, and L. Barkholt A comparison between low intensity and reduced intensity conditioning in allogeneic hematopoietic stem cell transplantation for solid tumors Haematologica, February 1, 2008; 93(2): 265 - 272. [Abstract] [Full Text] [PDF] I. Atreya, C. C Schimanski, C. Becker, S. Wirtz, H. Dornhoff, E. Schnurer, M. R Berger, P. R Galle, W. Herr, and M. F Neurath The T-box transcription factor eomesodermin controls CD8 T cell activity and lymph node metastasis in human colorectal cancer Gut, November 1, 2007; 56(11): 1572 - 1578. [Abstract] [Full Text] [PDF] T. C. Wehler, M. Nonn, B. Brandt, C. M. Britten, M. Grone, M. Todorova, I. Link, S. A. Khan, R. G. Meyer, C. Huber, et al. Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines Blood, January 1, 2007; 109(1): 365 - 373. [Abstract] [Full Text] [PDF] R. G. Meyer, C. M. Britten, D. Wehler, K. Bender, G. Hess, A. Konur, U. F. Hartwig, T. C. Wehler, A. J. Ullmann, C. Gentilini, et al. Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell-depleted reduced-intensity transplantation Blood, January 1, 2007; 109(1): 374 - 382. [Abstract] [Full Text] [PDF] S. Kausche, T. Wehler, E. Schnurer, V. Lennerz, W. Brenner, S. Melchior, M. Grone, M. Nonn, S. Strand, R. Meyer, et al. Superior Antitumor In vitro Responses of Allogeneic Matched Sibling Compared with Autologous Patient CD8+ T Cells Cancer Res., December 1, 2006; 66(23): 11447 - 11454. [Abstract] [Full Text] [PDF] S. Hofmann, M. Gluckmann, S. Kausche, A. Schmidt, C. Corvey, R. Lichtenfels, C. Huber, C. Albrecht, M. Karas, and W. Herr Rapid and Sensitive Identification of Major Histocompatibility Complex Class I-associated Tumor Peptides by Nano-LC MALDI MS/MS Mol. Cell. Proteomics, December 1, 2005; 4(12): 1888 - 1897. [Abstract] [Full Text] [PDF]

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