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 Blood, 1 November 2005, Vol. 106, No. 9, pp. 3223-3226.
Prepublished online as a Blood First Edition Paper on July 12, 2005; DOI 10.1182/blood-2005-04-1742.

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NEOPLASIA
Brief report

Transduction of CLL cells by CD40 ligand enhances an antigen-specific immune recognition by autologous T cells

Christine Mayr, David M. Kofler, Hildegard Büning, Dagmar Bund, Michael Hallek, and Clemens-Martin Wendtner

From the KKG Gene Therapy, GSF-National Research Center for Environment and Health, Munich; Medical Clinic III, Klinikum Grosshadern Medical Center, Ludwig-Maximilians-University, Munich; Medical Clinic I, University of Cologne, Cologne; and Gene Center, Ludwig-Maximilians-University, Munich, Germany.

Several features of chronic lymphocytic leukemia (CLL) suggest that immune-based strategies may have therapeutic potential. A promising approach is provided by the transduction of CLL cells with CD40 ligand (CD40L) by viral vectors to enhance their immunogenicity. We compared the antigen-presenting capacity of CD40L-transduced CLL cells with mock-transduced or CD40L-stimulated CLL cells (CD40-CLL). A significantly higher number of T cells could be expanded using CD40L-transduced CLL cells as antigen-presenting cells (APCs) compared with the control group (P = .008). Using 5 different CLL-associated tumor antigens, including fibromodulin, MDM2 (murine double minute 2), survivin, p53, and KW-13, we show in interferon-{gamma} (IFN-{gamma}) enzyme-linked immunospot (ELISPOT) assays after 35 days of in vitro culture that the number of antigen-specific autologous T cells was also significantly higher when CD40L-transduced CLL cells were used as APCs (P < .001). Thus, CD40L-transduced CLL cells are able to induce an antigen-specific T-cell response and might be superior to CD40-CLL cells for immune-based therapeutic strategies in CLL.


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A. P. Kater, M. H. J. van Oers, and T. J. Kipps
Cellular immune therapy for chronic lymphocytic leukemia
Blood, October 15, 2007; 110(8): 2811 - 2818.
[Abstract] [Full Text] [PDF]


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