SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-11-3601. This Article Full Text (PDF) All Versions of this Article: 2002-11-3601v1 102/1/284    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 Zhang, Z. Articles by Waldmann, T. A Search for Related Content PubMed PubMed Citation Articles by Zhang, Z. Articles by Waldmann, T. A Social Bookmarking                   What's this? Submitted December 2, 2002 Accepted February 24, 2003 Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD2 monoclonal antibody, MEDI-507 Zhuo Zhang, Meili Zhang, Jeffrey V Ravetch, Carolyn Goldman, and Thomas A Waldmann* Metabolism Branch, National Cancer Institute/NIH, Bethesda, MD, USA Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY, USA * Corresponding author; email: tawald{at}helix.nih.gov. Adult T-cell Leukemia (ATL) develops in a small proportion of individuals infected with the retrovirus HTLV-1. We evaluated the efficacy of MEDI-507 (a humanized monoclonal antibody directed against CD2) alone and in combination with humanized anti-Tac (HAT) directed toward CD25, the IL-2R, using a human Adult T-cell Leukemia xenograft model. Four-weekly treatments with HAT significantly prolonged the survival of the ATL bearing mice when compared to PBS treated controls (P < 0.0001). Mice treated with MEDI-507 (100 µg/week) for four weeks survived longer than those treated with HAT (P < 0.0025). Furthermore prolonged treatment (6 months) of ATL with MEDI-507 significantly improved the outcome when compared with that using a short course (4 weeks) of therapy (P < 0.0036). Such treatment with weekly MEDI-507 for six months led to a prolonged survival of the ATL bearing mice that was comparable to the survival observed in the control group of mice that did not receive a tumor or therapeutic agent. We also found that the expression of Fc receptors (FcR) on polymorphonuclear leukocytes and monocytes was required for MEDI-507 mediated tumor killing in vivo. Thus the tumor-killing mechanism with MEDI-507 in vivo required the expression of the receptor, FcRIII on polymorphonuclear leukocytes and monocytes suggesting that it is mediated by a form of antibody-dependent cellular cytotoxicity. These results demonstrate that MEDI-507 has therapeutic efficacy on ATL in vivo and provides support for a clinical trial involving this monoclonal antibody in the treatment of patients with CD2 expressing leukemias and lymphomas. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. O'Mahony, J. C. Morris, M. Stetler-Stevenson, H. Matthews, M. R. Brown, T. Fleisher, S. Pittaluga, M. Raffeld, P. S. Albert, D. Reitsma, et al. EBV-Related Lymphoproliferative Disease Complicating Therapy with the Anti-CD2 Monoclonal Antibody, Siplizumab, in Patients with T-Cell Malignancies Clin. Cancer Res., April 1, 2009; 15(7): 2514 - 2522. [Abstract] [Full Text] [PDF] Z. Zhang, M. Zhang, K. Garmestani, V. S. Talanov, P. S. Plascjak, B. Beck, C. Goldman, M. W. Brechbiel, and T. A. Waldmann Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25 Blood, August 1, 2006; 108(3): 1007 - 1012. [Abstract] [Full Text] [PDF] M. Zhang, Z. Yao, Z. Zhang, K. Garmestani, C. K. Goldman, J. V. Ravetch, J. Janik, M. W. Brechbiel, and T. A. Waldmann Effective therapy for a murine model of human anaplastic large-cell lymphoma with the anti-CD30 monoclonal antibody, HeFi-1, does not require activating Fc receptors Blood, July 15, 2006; 108(2): 705 - 710. [Abstract] [Full Text] [PDF] M. Zhang, Z. Zhang, C. K. Goldman, J. Janik, and T. A. Waldmann Combination therapy for adult T-cell leukemia-xenografted mice: flavopiridol and anti-CD25 monoclonal antibody Blood, February 1, 2005; 105(3): 1231 - 1236. [Abstract] [Full Text] [PDF] M. Zhang, Z. Zhang, K. Garmestani, C. K. Goldman, J. V. Ravetch, M. W. Brechbiel, J. A. Carrasquillo, and T. A. Waldmann Activating Fc Receptors Are Required for Antitumor Efficacy of the Antibodies Directed toward CD25 in a Murine Model of Adult T-Cell Leukemia Cancer Res., August 15, 2004; 64(16): 5825 - 5829. [Abstract] [Full Text] [PDF] I. C. Moura, Y. Lepelletier, B. Arnulf, P. England, C. Baude, C. Beaumont, A. Bazarbachi, M. Benhamou, R. C. Monteiro, and O. Hermine A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients Blood, March 1, 2004; 103(5): 1838 - 1845. [Abstract] [Full Text] [PDF]

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