SEARCH:   Advanced

Blood, 15 October 2006, Vol. 108, No. 8, pp. 2662-2668. Prepublished online as a Blood First Edition Paper on June 15, 2006; DOI 10.1182/blood-2006-04-017566. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-017566v1 108/8/2662    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Hirano, N. Articles by Nadler, L. M. Search for Related Content PubMed PubMed Citation Articles by Hirano, N. Articles by Nadler, L. M. Related Collections Immunobiology Neoplasia Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Identification of an immunogenic CD8+ T-cell epitope derived from -globin, a putative tumor-associated antigen for juvenile myelomonocytic leukemia Naoto Hirano, Marcus O. Butler, Zhinan Xia, Alla Berezovskaya, Andrew P. Murray, Sascha Ansén, Seiji Kojima, and Lee M. Nadler From the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Medicine, Brigham and Women's Hospital, Boston, MA; the Department of Medicine, Harvard Medical School, Boston, MA; and the Department of Pediatrics, Nagoya University, Japan. Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disorder. Although allogeneic stem cell transplantation can induce long-term remissions, relapse rates remain high and innovative approaches are needed. Since donor lymphocyte infusions have clinical activity in JMML, T-cell-mediated immunotherapy could provide a nonredundant treatment approach to compliment current therapies. -Globin, an oncofetal protein overexpressed by clonogenic JMML cells, may serve as a target of an antitumor immune response. We predicted 5 -globin-derived peptides as potential human leukocyte antigen (HLA)-A2 restricted cytotoxic T lymphocyte (CTL) epitopes and showed that 4 (g031, g071, g105, and g106) bind A2 molecules in vitro. Using an artificial antigen-presenting cell (aAPC) that can process both the N- and C-termini of endogenously expressed proteins, we biochemically confirmed that g105 is naturally processed and presented by cell surface A2. Furthermore, g105-specific CD8+ CTLs generated from A2-positive healthy donors were able to specifically cytolyze -globin+, but not -globin- JMML cells in an A2-restricted manner. These results suggest that this aAPC-based approach enables the biochemical identification of CD8+ T-cell epitopes that are processed and presented by intact cells, and that CTL immunotherapy of JMML could be directed against the -globin-derived epitope g105. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Komita, X. Zhao, J. L. Taylor, L. J. Sparvero, A. A. Amoscato, S. Alber, S. C. Watkins, A. D. Pardee, A. K. Wesa, and W. J. Storkus CD8+ T-Cell Responses against Hemoglobin-{beta} Prevent Solid Tumor Growth Cancer Res., October 1, 2008; 68(19): 8076 - 8084. [Abstract] [Full Text] [PDF] S. Ansen, M. O. Butler, A. Berezovskaya, A. P. Murray, K. Stevenson, L. M. Nadler, and N. Hirano Dissociation of Its Opposing Immunologic Effects Is Critical for the Optimization of Antitumor CD8+ T-Cell Responses Induced by Interleukin 21 Clin. Cancer Res., October 1, 2008; 14(19): 6125 - 6136. [Abstract] [Full Text] [PDF] S. M. Domchek, A. Recio, R. Mick, C. E. Clark, E. L. Carpenter, K. R. Fox, A. DeMichele, L. M. Schuchter, M. S. Leibowitz, M. H. Wexler, et al. Telomerase-Specific T-Cell Immunity in Breast Cancer: Effect of Vaccination on Tumor Immunosurveillance Cancer Res., November 1, 2007; 67(21): 10546 - 10555. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020