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Mayr, C. ; Bund, D. ; Schlee, M. ; Moosmann, A.* ; Kofler, D.M. ; Hallek, M. ; Wendtner, C.-M.

Fibromodulin as a novel tumor-associated antigen (TAA)in chronic lymphocytic leukemia (CLL) which allows expansion of specific CD8+ autologous T lymphocytes.

Blood 105, 1566-1573 (2005)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Fibromodulin (FMOD) was shown to be highly overexpressed in chronic lymphocytic leukemia (CLL) cells compared with 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 reverse transcriptase–polymerase chain reaction (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 (APCs) to expand autologous T cells from 13 patients. The number of T cells during 4 weeks of in vitro culture increased 2- to 3.5-fold and the number of T cells recognizing FMOD peptides bound to HLA-A2 dimers increased 10-fold. The expanded T cells also were able to secrete interferon-γ (IFN-γ) upon recognition of the antigen demonstrated by IFN-γ ELISPOT assays. T cells not only recognized HLA-A2–binding FMOD peptides presented by transporter-associated with antigen-processing (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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 105, Issue: 4, Pages: 1566-1573 Article Number: , Supplement: ,
Publisher American Society of Hematology
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)