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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1566-1573.
Prepublished online as a Blood First Edition Paper on October 7, 2004; DOI 10.1182/blood-2004-04-1233.
Previous Article | Next Article 
Submitted April 1, 2004
Accepted September 30, 2004
Fibromodulin as a novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (CLL) which allows expansion of specific CD8+ autologous T lymphocytes
Christine Mayr, Dagmar Bund, Martin Schlee, Andreas Moosmann, David M Kofler, Michael Hallek, and Clemens-Martin Wendtner*
KKG Gene Therapy, GSF-National Research Center for Environment and Health, Munich, Germany; Medical Clinic III, Klinikum Grosshadern Medical Center (KGMC), Ludwig-Maximilians-University, Munich, Germany
KKG Gene Therapy, GSF-National Research Center for Environment and Health, Munich, Germany
Clinical Molecular Biology and Tumor Genetics, GSF-National Research Center for Environment and Health, Munich, Germany
Department of Otorhinolaryngology, Ludwig-Maximilians-University, Munich, Germany
KKG Gene Therapy, GSF-National Research Center for Environment and Health, Munich, Germany; Medical Clinic III, Klinikum Grosshadern Medical Center (KGMC), Ludwig-Maximilians-University, Munich, Germany; Medical Clinic I, University of Cologne, Cologne, Germany
* Corresponding author; email: Clemens.Wendtner{at}uni-koeln.de.
Fibromodulin (FMOD) was shown to be highly overexpressed in CLL cells compared to normal B lymphocytes by gene expression profiling. Therefore FMOD might serve as potential tumor associated antigen (TAA) in CLL enabling expansion of FMOD-specific T cells. In CLL samples derived from 16 different patients, high expression of FMOD by real-time RT-PCR was detectable in contrast to normal B lymphocytes. We used unpulsed native CLL cells and CD40 ligand (CD40L) stimulated CLL cells as antigen presenting cells (APC) to expand autologous T cells from 13 patients. The number of T cells during four weeks of in vitro culture increased 2 to 3.5-fold and the amount of T cells recognizing FMOD peptides bound to HLA-A2-dimers increased 10-fold. The expanded T cells were also able to secrete IFN- upon recognition of the antigen demonstrated by IFN- -ELISPOT assays. T cells not only recognized HLA-A2 binding FMOD peptides presented by TAP-deficient T2 cells, but also FMOD overexpressing autologous CLL cells in an HLA-A2 restricted manner. In summary, FMOD was shown for the first time to be naturally processed and presented as TAA in primary CLL cells enabling the expansion of autologous tumor-specific T cells.

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