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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2736-2744. Prepublished online as a Blood First Edition Paper on June 15, 2006; DOI 10.1182/blood-2006-04-017921. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-017921v1 108/8/2736    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 Stein, R. Articles by Goldenberg, D. M. Search for Related Content PubMed PubMed Citation Articles by Stein, R. Articles by Goldenberg, D. M. Related Collections Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Characterization of a humanized IgG4 anti-HLA-DR monoclonal antibody that lacks effector cell functions but retains direct antilymphoma activity and increases the potency of rituximab Rhona Stein, Zhengxing Qu, Susan Chen, David Solis, Hans J. Hansen, and David M. Goldenberg From the Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ; and Immunomedics, Morris Plains, NJ. HLA-DR is under investigation as a target for monoclonal antibody (mAb) therapy of malignancies. Here we describe a humanized IgG4 form of the anti-HLA-DR mAb L243, hL2434P (IMMU-114), generated to provide an agent with selectivity toward neoplastic cells that can kill without complement-dependent cytotoxicity (CDC) or antibody-dependent cellular-cytotoxicity (ADCC), so as to reduce reliance on intact immunologic systems in the patient and effector mechanism-related toxicity. In vitro studies show that replacing the Fc region of hL2431, a humanized IgG1 anti-HLA-DR mAb, with the IgG4 isotype abrogates the effector cell functions of the antibody (ADCC and CDC) while retaining its antigen-binding properties, antiproliferative capacity (in vitro and in vivo), and the ability to induce apoptosis concurrent with activation of the AKT survival pathway. Growth inhibition was evaluated compared with and in combination with the anti-CD20 mAb rituximab, with the combination being more effective than rituximab alone in inhibiting proliferation. Thus, hL2434P is indistinguishable from hL2431 and the parental murine mAb in assays dependent on antigen recognition. The abrogation of ADCC and CDC, which are believed to play a major role in side effects of mAb therapy, may make this antibody an attractive clinical agent. In addition, combination of hL2434P with rituximab offers the prospect for improved patient outcome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. A. Rossi, D. M. Goldenberg, T. M. Cardillo, R. Stein, and C.-H. Chang CD20-targeted tetrameric interferon-{alpha}, a novel and potent immunocytokine for the therapy of B-cell lymphomas Blood, October 29, 2009; 114(18): 3864 - 3871. [Abstract] [Full Text] [PDF] B. D. Cheson and J. P. Leonard Monoclonal Antibody Therapy for B-Cell Non-Hodgkin's Lymphoma N. Engl. J. Med., August 7, 2008; 359(6): 613 - 626. [Full Text] [PDF] P. Martin, R. R. Furman, M. Coleman, and J. P. Leonard Phase I to III Trials of Anti B Cell Therapy in Non Hodgkin's Lymphoma Clin. Cancer Res., September 15, 2007; 13(18): 5636s - 5642s. [Abstract] [Full Text] [PDF]

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