SEARCH:   Advanced

Blood, 1 March 2004, Vol. 103, No. 5, pp. 1838-1845. Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-07-2440. This Article Full Text (PDF) All Versions of this Article: 2003-07-2440v1 103/5/1838    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 Moura, I. C Articles by Hermine, O. Search for Related Content PubMed PubMed Citation Articles by Moura, I. C Articles by Hermine, O. Social Bookmarking                   What's this? Submitted July 18, 2003 Accepted October 16, 2003 A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients Ivan C Moura, Yves Lepelletier, Bertrand Arnulf, Patrick England, Cedric Baude, Carole Beaumont, Ali Bazarbachi, Marc Benhamou, Renato C Monteiro, and Olivier Hermine* Department of Immunopathology, Bichat Medical School, Inserm E0225, Paris, France Department of Immunohematology, Necker Hospital, CNRS FRE-2444, Paris, France Plateforme de Biophysique des Macromolecules et de leurs Interactions, Pasteur Institute, Paris, France Bichat Medical School, Inserm U409, Paris, France Departments of Internal Medicine and Biochemistry, American University of Beirut, Beirut, Lebanon * Corresponding author; email: hermine{at}necker.fr. ATL (adult T-cell leukemia/lymphoma) is an aggressive lymphoid proliferative disease that exists under diverse clinical forms ranging from chronic to acute. Although leukemic cells from ATL patients exhibit an intrinsic resistance to chemotherapy, monoclonal antibodies directed against CD25 (IL-2R-Ab) have been used as specific therapeutic agents. However, significant clinical results with these Abs have been demonstrated only in chronic forms of ATL. In contrast to resting T cells, HTLV-I-infected cells constitutively express high levels of surface transferrin receptor (TfR). Herein, we report the characterization of a new monoclonal antibody (mAb A24), directed against the human TfR, and the evaluation of its capacity to block the proliferation of ATL cells ex vivo. We determined that A24 binds TfR with a Kd of 2.7 nM, and competes with transferrin for binding to TfR. A24 also inhibited [55Fe]-transferrin uptake in activated T cells and blocked T cell proliferation. Moreover, A24 reduced and impaired TfR expression and recycling, respectively. Most importantly, we showed that A24 blocked the ex vivo proliferation of malignant T cells from both acute and chronic forms of ATL, through induction of programmed cell death. Therefore efficient therapeutic tools to treat acute forms of ATL might be derived from A24. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Tsukasaki, O. Hermine, A. Bazarbachi, L. Ratner, J. C. Ramos, W. Harrington Jr, D. O'Mahony, J. E. Janik, A. L. Bittencourt, G. P. Taylor, et al. Definition, Prognostic Factors, Treatment, and Response Criteria of Adult T-Cell Leukemia-Lymphoma: A Proposal From an International Consensus Meeting J. Clin. Oncol., January 20, 2009; 27(3): 453 - 459. [Abstract] [Full Text] [PDF] T. Matysiak-Budnik, I. C. Moura, M. Arcos-Fajardo, C. Lebreton, S. Menard, C. Candalh, K. Ben-Khalifa, C. Dugave, H. Tamouza, G. van Niel, et al. Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease J. Exp. Med., January 21, 2008; 205(1): 143 - 154. [Abstract] [Full Text] [PDF] Y. Lepelletier, V. Camara-Clayette, H. Jin, A. Hermant, S. Coulon, M. Dussiot, M. Arcos-Fajardo, C. Baude, D. Canionni, R. Delarue, et al. Prevention of Mantle Lymphoma Tumor Establishment by Routing Transferrin Receptor toward Lysosomal Compartments Cancer Res., February 1, 2007; 67(3): 1145 - 1154. [Abstract] [Full Text] [PDF] P. P. Ng, G. Helguera, T. R. Daniels, S. Z. Lomas, J. A. Rodriguez, G. Schiller, B. Bonavida, S. L. Morrison, and M. L. Penichet Molecular events contributing to cell death in malignant human hematopoietic cells elicited by an IgG3-avidin fusion protein targeting the transferrin receptor Blood, October 15, 2006; 108(8): 2745 - 2754. [Abstract] [Full Text] [PDF] D. T. Jones, I. S. Trowbridge, and A. L. Harris Effects of transferrin receptor blockade on cancer cell proliferation and hypoxia-inducible factor function and their differential regulation by ascorbate. Cancer Res., March 1, 2006; 66(5): 2749 - 2756. [Abstract] [Full Text] [PDF] M. A. Rizvi, A. M. Evens, M. S. Tallman, B. P. Nelson, and S. T. Rosen T-cell non-Hodgkin lymphoma Blood, February 15, 2006; 107(4): 1255 - 1264. [Abstract] [Full Text] [PDF] B. N. Stillman, D. K. Hsu, M. Pang, C. F. Brewer, P. Johnson, F.-T. Liu, and L. G. Baum Galectin-3 and Galectin-1 Bind Distinct Cell Surface Glycoprotein Receptors to Induce T Cell Death J. Immunol., January 15, 2006; 176(2): 778 - 789. [Abstract] [Full Text] [PDF] I. C. Moura, M. Arcos-Fajardo, A. Gdoura, V. Leroy, C. Sadaka, N. Mahlaoui, Y. Lepelletier, F. Vrtovsnik, E. Haddad, M. Benhamou, et al. Engagement of Transferrin Receptor by Polymeric IgA1: Evidence for a Positive Feedback Loop Involving Increased Receptor Expression and Mesangial Cell Proliferation in IgA Nephropathy J. Am. Soc. Nephrol., September 1, 2005; 16(9): 2667 - 2676. [Abstract] [Full Text] [PDF] G. Regis, M. Bosticardo, L. Conti, S. De Angelis, D. Boselli, B. Tomaino, P. Bernabei, M. Giovarelli, and F. Novelli Iron regulates T-lymphocyte sensitivity to the IFN-{gamma}/STAT1 signaling pathway in vitro and in vivo Blood, April 15, 2005; 105(8): 3214 - 3221. [Abstract] [Full Text] [PDF] B. Pasquier, Y. Lepelletier, C. Baude, O. Hermine, and R. C. Monteiro Differential expression and function of IgA receptors (CD89 and CD71) during maturation of dendritic cells J. Leukoc. Biol., December 1, 2004; 76(6): 1134 - 1141. [Abstract] [Full Text] [PDF]

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