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

Abstract

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-gamma (IFN-gamma) upon recognition of the antigen demonstrated by IFN-gamma 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.

• Authors: Christine Mayr, Dagmar Bund, Martin Schlee, Andreas Moosmann, David M Kofler, Michael Hallek, Clemens-Martin Wendtner
• Journal: Blood (Blood) Vol. 105 Issue 4 Pg. 1566-73 (Feb 15 2005) ISSN: 0006-4971 [Print] United States
• PMID: 15471955 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Epitopes, T-Lymphocyte
• Extracellular Matrix Proteins
• FMOD protein, human
• HLA-A2 Antigen
• Peptide Fragments
• Proteoglycans
• RNA, Messenger
• Fibromodulin
• CD40 Ligand

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigen Presentation
• Antigen-Presenting Cells (immunology, metabolism, pathology)
• Antigens, Neoplasm (biosynthesis, genetics, immunology, metabolism)
• CD40 Ligand (pharmacology)
• CD8-Positive T-Lymphocytes (immunology, metabolism, pathology)
• Cell Line, Transformed
• Cell Line, Tumor
• Dimerization
• Enzyme-Linked Immunosorbent Assay
• Epitopes, T-Lymphocyte (immunology, metabolism)
• Extracellular Matrix Proteins (biosynthesis, genetics, immunology, metabolism)
• Female
• Fibromodulin
• HLA-A2 Antigen (immunology, metabolism)
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (immunology, pathology)
• Lymphocyte Activation (immunology)
• Male
• Middle Aged
• Peptide Fragments (immunology, metabolism)
• Proteoglycans (biosynthesis, genetics, immunology, metabolism)
• RNA, Messenger (biosynthesis)
• Staining and Labeling