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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3127-3133. Prepublished online as a Blood First Edition Paper on July 21, 2005; DOI 10.1182/blood-2005-06-2298. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: 2005-06-2298v1 106/9/3127    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 Lute, K. D. Articles by Liu, Y. Search for Related Content PubMed PubMed Citation Articles by Lute, K. D. Articles by Liu, Y. Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Human CTLA4 knock-in mice unravel the quantitative link between tumor immunity and autoimmunity induced by anti–CTLA-4 antibodies Kenneth D. Lute, Kenneth F. May, Jr, Ping Lu, Huiming Zhang, Ergun Kocak, Bedrick Mosinger, Christopher Wolford, Gary Phillips, Michael A. Caligiuri, Pan Zheng, and Yang Liu From the Division of Cancer Immunology, the Department of Pathology, the Center for Biostatistics, the Neurobiotechnology Center, and the Department of Internal Medicine, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH. Although results from preclinical studies in animal models have proven the concept for use of anti–cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies in cancer immunotherapy, 2 major obstacles have hindered their successful application for human cancer therapy. First, the lack of in vitro correlates of the antitumor effect of the antibodies makes it difficult to screen for the most efficacious antibody by in vitro analysis. Second, significant autoimmune side effects have been observed in a recent clinical trial. In order to address these 2 issues, we have generated human CTLA4 gene knock-in mice and used them to compare a panel of anti–human CTLA-4 antibodies for their ability to induce tumor rejection and autoimmunity. Surprisingly, while all antibodies induced protection against cancer and demonstrated some autoimmune side effects, the antibody that induced the strongest protection also induced the least autoimmune side effects. These results demonstrate that autoimmune disease does not quantitatively correlate with cancer immunity. Our approach may be generally applicable to the development of human therapeutic antibodies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Gattinoni, A. Ranganathan, D. R. Surman, D. C. Palmer, P. A. Antony, M. R. Theoret, D. M. Heimann, S. A. Rosenberg, and N. P. Restifo CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent Blood, December 1, 2006; 108(12): 3818 - 3823. [Abstract] [Full Text] [PDF] E. Kocak, K. Lute, X. Chang, K. F. May Jr., K. R. Exten, H. Zhang, S. F. Abdessalam, A. M. Lehman, D. Jarjoura, P. Zheng, et al. Combination Therapy with Anti-CTL Antigen-4 and Anti-4-1BB Antibodies Enhances Cancer Immunity and Reduces Autoimmunity. Cancer Res., July 15, 2006; 66(14): 7276 - 7284. [Abstract] [Full Text] [PDF] S. Tartz, J. Kamanova, M. Simsova, P. Sebo, S. Bolte, V. Heussler, B. Fleischer, and T. Jacobs Immunization with a Circumsporozoite Epitope Fused to Bordetella pertussis Adenylate Cyclase in Conjunction with Cytotoxic T-Lymphocyte-Associated Antigen 4 Blockade Confers Protection against Plasmodium berghei Liver-Stage Malaria Infect. Immun., April 1, 2006; 74(4): 2277 - 2285. [Abstract] [Full Text] [PDF]

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