SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2002-11-3584. This Article Full Text (PDF) All Versions of this Article: 2002-11-3584v1 102/8/2885    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 de Rijke, B. Articles by Dolstra, H. Search for Related Content PubMed PubMed Citation Articles by de Rijke, B. Articles by Dolstra, H. Social Bookmarking                   What's this? Submitted November 26, 2002 Accepted June 10, 2003 Generation of autologous cytotoxic and helper T-cell responses against the B-cell leukemia-associated antigen HB-1: relevance for precursor B-ALL-specific immunotherapy Bjorn de Rijke, Hanny Fredrix, Agnes Zoetbrood, Frank Scherpen, Henry Witteveen, Theo de Witte, Elly van de Wiel-van Kemenade, and Harry Dolstra* Central Hematology Laboratory, University Medical Center St. Radboud, Nijmegen, The Netherlands Department of Hematology, University Medical Center St. Radboud, Nijmegen, The Netherlands * Corresponding author; email: h.dolstra{at}chl.umcn.nl. Tumor relapses in patients with precursor B acute lymphoblastic leukemia (B-ALL) occur frequently after primary treatment. Therefore, development of additional treatment modalities to eliminate residual tumor cells are needed. Active immunotherapy using dendritic cells (DC) loaded with tumor-associated antigens is a promising approach to induce specific T cell immunity in cancer patients. In previous studies, we described HB-1 as a B cell lineage-specific antigen that is recognized by donor-derived cytotoxic T lymphocytes (CTL) on allogeneic B-ALL tumor cells. Here, we investigated the potential use of the HB-1 antigen as an autologous T cell vaccine target. To determine whether HB-1-specific CTL precursors are present within the T cell repertoire, we induced expansion of CD8+ T cells using mature monocyte-derived DC pulsed with the previously identified HB-1.B44 antigenic peptide. In six out of eight donors, CD8+ CTL lines have been generated that exert cytotoxicity against target cells exogenously pulsed with peptide or endogenously expressing the HB-1 antigen. From one of these HB-1-specific T cell lines, we isolated a CD8+ CTL that produces IFN- upon stimulation with B-ALL tumor cells. Interestingly, the HB-1 antigen also induced CD4+ T helper responses upon activation with protein-loaded mature monocyte-derived DC. We identified two novel epitopes recognized in the context of HLA-DR4 and HLA-DR11 using HB-1-specific CD4+ T cell clones generated from different donors. The present data, that HB-1 induces both helper and cytotoxic T cell responses, indicates that the HB-1 antigen is a candidate target to induce T cell-mediated antitumor immunity in patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. N. Haining, D. S. Neuberg, H. L. Keczkemethy, J. W. Evans, S. Rivoli, R. Gelman, H. M. Rosenblatt, W. T. Shearer, J. Guenaga, D. C. Douek, et al. Antigen-specific T-cell memory is preserved in children treated for acute lymphoblastic leukemia Blood, September 1, 2005; 106(5): 1749 - 1754. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020