SEARCH:   Advanced

Blood, 15 March 2005, Vol. 105, No. 6, pp. 2436-2442. Prepublished online as a Blood First Edition Paper on November 9, 2004; DOI 10.1182/blood-2004-07-2556. This Article Full Text (PDF) All Versions of this Article: 2004-07-2556v1 105/6/2436    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 Biagi, E. Articles by Brenner, M. Search for Related Content PubMed PubMed Citation Articles by Biagi, E. Articles by Brenner, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 8, 2004 Accepted November 5, 2004 Molecular transfer of CD40 and OX40 ligands to leukemic human B-cells induces expansion of autologous tumor-reactive cytotoxic T-lymphocytes Ettore Biagi*, Gianpietro Dotti, Eric Yvon, Edward Lee, Martin Pule, Stephane Vigouroux, Stephen Gottschalk, Uday Popat, Raphael Rousseau, and Malcolm Brenner Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA * Corresponding author; email: exbiagi{at}txccc.org. Clinical benefits from monoclonal antibody therapy for B-Chronic Lymphocytic Leukemia (B-CLL) have increased interest in developing additional immunotherapies for the disease. CD40 ligand is an accessory signal for T-cell activation and can overcome T-cell anergy. The OX40-OX40 ligand pathway is involved in the subsequent expansion of memory antigen-specific T cells. We expressed both CD40L and OX40L on B-CLL cells, by exploiting the phenomenon of molecular transfer from fibroblasts over-expressing these ligands. We analyzed the effects of the modified B-CLL cells on the number, phenotype and cytotoxic function of autologous T cells in seven B-CLL patients. Transfer of CD40L and OX40L was observed in all and was followed by up-regulation of B7-1 and B7-2. The culture of CD40L/OX40L-expressing B-CLL cells with autologous T cells generated CD4+/CD8+ cytotoxic T-cell lines, which secreted IFN- and granzyme-B/perforin in response to autologous, but not to allogeneic B-CLL cells or to autologous T-cell blasts. Either CD40L or OX40L alone were insufficient to expand tumor-reactive T cells. The combination of CD40L and OX40L on B-CLL cells may allow generation of therapeutic immune responses to B-CLL, either by active immunization with modified tumor cells or by adoptive immunotherapy with tumor-reactive autologous T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Hirschhorn-Cymerman, G. A. Rizzuto, T. Merghoub, A. D. Cohen, F. Avogadri, A. M. Lesokhin, A. D. Weinberg, J. D. Wolchok, and A. N. Houghton OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis J. Exp. Med., May 11, 2009; 206(5): 1103 - 1116. [Abstract] [Full Text] [PDF] B. E. Burrell, G. Lu, X. C. Li, and D. K. Bishop OX40 Costimulation Prevents Allograft Acceptance Induced by CD40-CD40L Blockade J. Immunol., January 1, 2009; 182(1): 379 - 390. [Abstract] [Full Text] [PDF] S. Murata, B. H. Ladle, P. S. Kim, E. R. Lutz, M. E. Wolpoe, S. E. Ivie, H. M. Smith, T. D. Armstrong, L. A. Emens, E. M. Jaffee, et al. OX40 Costimulation Synergizes with GM-CSF Whole-Cell Vaccination to Overcome Established CD8+ T Cell Tolerance to an Endogenous Tumor Antigen J. Immunol., January 15, 2006; 176(2): 974 - 983. [Abstract] [Full Text] [PDF] L. Serghides, J. Bukczynski, T. Wen, C. Wang, J.-P. Routy, M.-R. Boulassel, R.-P. Sekaly, M. Ostrowski, N. F. Bernard, and T. H. Watts Evaluation of OX40 Ligand as a Costimulator of Human Antiviral Memory CD8 T Cell Responses: Comparison with B7.1 and 4-1BBL J. Immunol., November 15, 2005; 175(10): 6368 - 6377. [Abstract] [Full Text] [PDF] C. Palena, K. A. Foon, D. Panicali, A. G. Yafal, J. Chinsangaram, J. W. Hodge, J. Schlom, and K. Y. Tsang Potential approach to immunotherapy of chronic lymphocytic leukemia (CLL): enhanced immunogenicity of CLL cells via infection with vectors encoding for multiple costimulatory molecules Blood, November 15, 2005; 106(10): 3515 - 3523. [Abstract] [Full Text] [PDF] E. Biagi, R. Rousseau, E. Yvon, M. Schwartz, G. Dotti, A. Foster, D. Havlik-Cooper, B. Grilley, A. Gee, K. Baker, et al. Responses to Human CD40 Ligand/Human Interleukin-2 Autologous Cell Vaccine in Patients with B-Cell Chronic Lymphocytic Leukemia Clin. Cancer Res., October 1, 2005; 11(19): 6916 - 6923. [Abstract] [Full Text] [PDF] J. Zhou, Y. Tagaya, R. Tolouei-Semnani, J. Schlom, and H. Sabzevari Physiological relevance of antigen presentasome (APS), an acquired MHC/costimulatory complex, in the sustained activation of CD4+ T cells in the absence of APCs Blood, April 15, 2005; 105(8): 3238 - 3246. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020