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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3515-3523. Prepublished online as a Blood First Edition Paper on August 4, 2005; DOI 10.1182/blood-2005-03-1214. This Article Full Text (PDF) All Versions of this Article: 2005-03-1214v1 106/10/3515    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 Palena, C. Articles by Tsang, K. Y Search for Related Content PubMed PubMed Citation Articles by Palena, C. Articles by Tsang, K. Y Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 31, 2005 Accepted July 18, 2005 A potential approach to immunotherapy of chronic lymphocytic leukemia (CLL): enhanced immunogenicity of CLL cells via infection with vectors encoding for multiple costimulatory molecules Claudia Palena, Kenneth A Foon, Dennis Panicali, Alicia Gomez Yafal, Jarasvech Chinsangaram, James W Hodge, Jeffrey Schlom*, and Kwong Y Tsang Laboratory of Tumor Immunology and Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA Therion Biologics Corporation, Cambridge, MA, USA * Corresponding author; email: js141c{at}nih.gov. Chronic lymphocytic leukemia (CLL) is a disease of CD5+ B lymphocytes (designated as CLL cells) that are inefficient antigen-presenting cells. Their poor ability to present antigens to the T cells, largely due to an inadequate costimulatory capacity, is manifested as a failure to stimulate proliferation of both allogeneic and autologous T cells. We have investigated the ability of in vitro manipulated CLL cells, via hyperexpression of a triad of costimulatory molecules (B7-1, ICAM-1 and LFA-3, designated TRICOM), to stimulate effective anti-tumor T-cell responses. A recombinant Modified Vaccinia Virus strain Ankara (MVA), which is a highly attenuated, replication-impaired virus variant, was successfully used to infect and deliver the simultaneous expression of the 3 human costimulatory molecules in TRICOM on the surface of the CLL cells. Proliferation of allogeneic and autologous T cells was observed when MVA-TRICOM infected CLL cells were used as stimulators in proliferation assays. Cytotoxic T lymphocytes, generated in vitro by stimulation of autologous T cells with MVA-TRICOM-infected CLL cells, showed cytotoxicity against unmodified/uninfected CLL cells. Therefore, our findings suggest that the use of CLL cells infected ex vivo with MVA-TRICOM or direct injection of MVA-TRICOM in CLL patients has potential for the immunotherapy of CLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: MVA-TRICOM vaccine strategy makes CLL cells an attractive T-cell target John C. Byrd Blood 2005 106: 3334-3335. [Full Text] [PDF] This article has been cited by other articles: Y. Chung, H. Qin, C.-Y. Kang, S. Kim, L. W. Kwak, and C. Dong An NKT-mediated autologous vaccine generates CD4 T-cell dependent potent antilymphoma immunity Blood, September 15, 2007; 110(6): 2013 - 2019. [Abstract] [Full Text] [PDF] C. Palena, D. E. Polev, K. Y. Tsang, R. I. Fernando, M. Litzinger, L. L. Krukovskaya, A. V. Baranova, A. P. Kozlov, and J. Schlom The Human T-Box Mesodermal Transcription Factor Brachyury Is a Candidate Target for T-Cell-Mediated Cancer Immunotherapy Clin. Cancer Res., April 15, 2007; 13(8): 2471 - 2478. [Abstract] [Full Text] [PDF]

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