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Blood, 15 July 2005, Vol. 106, No. 2, pp. 470-476. Prepublished online as a Blood First Edition Paper on March 24, 2005; DOI 10.1182/blood-2004-09-3663. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-09-3663v1 106/2/470    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 Tsuji, T. Articles by Nishimura, T. Search for Related Content PubMed PubMed Citation Articles by Tsuji, T. Articles by Nishimura, T. Related Collections Immunobiology Immunotherapy Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Generation of tumor-specific, HLA class I–restricted human Th1 and Tc1 cells by cell engineering with tumor peptide–specific T-cell receptor genes Takemasa Tsuji, Masaki Yasukawa, Junko Matsuzaki, Takayuki Ohkuri, Kenji Chamoto, Daiko Wakita, Taichi Azuma, Hironari Niiya, Hiroyuki Miyoshi, Kiyotaka Kuzushima, Yoshihiro Oka, Haruo Sugiyama, Hiroaki Ikeda, and Takashi Nishimura From the Division of Immunoregulation, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan; the First Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan; the Subteam for Manipulation of Cell Fate, BioResource Center, RIKEN Tsukuba Institute, Ibaraki, Japan; the Division of Immunology, Aichi Cancer Center Research Institute, Aichi Cancer Center Hospital, Nagoya, Japan; the Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; and the Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan. Tumor antigen–specific CD4+ and CD8+ T lymphocytes, especially interferon- (IFN-)–producing type-1 helper T (Th1) and type-1 cytotoxic T (Tc1) cells, play a crucial role in tumor eradication. Adoptive transfer using tumor-specific Th1 and Tc1 cells is a promising therapeutic strategy for tumor immunotherapy. However, its clinical application has been hampered because of difficulties in generating tumor-specific Th1 cells from patients with tumors. To overcome this problem, we have developed an efficient method to prepare tumor-specific Th1 and Tc1 cells. T-cell receptor (TCR) and genes obtained from an HLA-A24–restricted, Wilms tumor 1 (WT1) peptide–specific Tc clone were lentivirally transduced to polyclonally activated Th1 and Tc1 cells. As expected, TCR gene-modified Tc1 cells showed cytotoxicity and IFN- production in response to peptide-loaded lymphoblastoid cell lines, WT1 gene–transduced cells, and freshly isolated leukemia cells expressing both WT1 and HLA-A24. Surprisingly, we further demonstrated that Th1 cells transduced with HLA-class I–restricted TCR genes also showed both cytotoxicity and cytokine production in an HLA-A24–restricted manner. In contrast to gene-modified Tc1 cells, Th1 cells produced high amounts of interleukin-2 (IL-2) in addition to IFN-, which is beneficial for induction of antitumor cellular immunity. Thus, TCR gene–modified HLA-class I–restricted Th1 and Tc1 cells are a powerful strategy for the application to adoptive immunotherapy of human cancer. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Chhabra, L. Yang, P. Wang, B. Comin-Anduix, R. Das, N. G. Chakraborty, S. Ray, S. Mehrotra, H. Yang, C. L. Hardee, et al. CD4+CD25- T Cells Transduced to Express MHC Class I-Restricted Epitope-Specific TCR Synthesize Th1 Cytokines and Exhibit MHC Class I-Restricted Cytolytic Effector Function in a Human Melanoma Model J. Immunol., July 15, 2008; 181(2): 1063 - 1070. [Abstract] [Full Text] [PDF] R. Spaapen, K. van den Oudenalder, R. Ivanov, A. Bloem, H. Lokhorst, and T. Mutis Rebuilding Human Leukocyte Antigen Class II-Restricted Minor Histocompatibility Antigen Specificity in Recall Antigen-Specific T Cells by Adoptive T Cell Receptor Transfer: Implications for Adoptive Immunotherapy Clin. Cancer Res., July 1, 2007; 13(13): 4009 - 4015. [Abstract] [Full Text] [PDF] J. Kuball, M. L. Dossett, M. Wolfl, W. Y. Ho, R.-H. Voss, C. Fowler, and P. D. Greenberg Facilitating matched pairing and expression of TCR chains introduced into human T cells Blood, March 15, 2007; 109(6): 2331 - 2338. [Abstract] [Full Text] [PDF] G. E. Lyons, T. Moore, N. Brasic, M. Li, J. J. Roszkowski, and M. I. Nishimura Influence of Human CD8 on Antigen Recognition by T-Cell Receptor-Transduced Cells Cancer Res., December 1, 2006; 66(23): 11455 - 11461. [Abstract] [Full Text] [PDF] R. A. Willemsen, Z. Sebestyen, C. Ronteltap, C. Berrevoets, J. Drexhage, and R. Debets CD8{alpha} Coreceptor to Improve TCR Gene Transfer to Treat Melanoma: Down-Regulation of Tumor-Specific Production of IL-4, IL-5, and IL-10 J. Immunol., July 15, 2006; 177(2): 991 - 998. [Abstract] [Full Text] [PDF] F. Nishimura, J. E. Dusak, J. Eguchi, X. Zhu, A. Gambotto, W. J. Storkus, and H. Okada Adoptive Transfer of Type 1 CTL Mediates Effective Anti-Central Nervous System Tumor Response: Critical Roles of IFN-Inducible Protein-10. Cancer Res., April 15, 2006; 66(8): 4478 - 4487. [Abstract] [Full Text] [PDF] K. Chamoto, D. Wakita, Y. Narita, Y. Zhang, D. Noguchi, H. Ohnishi, T. Iguchi, T. Sakai, H. Ikeda, and T. Nishimura An Essential Role of Antigen-Presenting Cell/T-Helper Type 1 Cell-Cell Interactions in Draining Lymph Node during Complete Eradication of Class II-Negative Tumor Tissue by T-Helper Type 1 Cell Therapy Cancer Res., February 1, 2006; 66(3): 1809 - 1817. [Abstract] [Full Text] [PDF]

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