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TCL1: a shared tumor-associated antigen for immunotherapy against B-cell lymphomas.
- Source :
-
Blood [Blood] 2012 Aug 23; Vol. 120 (8), pp. 1613-23. Date of Electronic Publication: 2012 May 29. - Publication Year :
- 2012
-
Abstract
- Immunotherapy with therapeutic idiotype vaccines offers promise for treatment of B-cell malignancies. However, identification of novel immunogenic lymphoma-associated antigens that are universally expressed is necessary to overcome the barriers of patient-specific idiotype vaccines. Here, we determined whether T-cell leukemia/lymphoma 1 (TCL1) oncoprotein encoded by the TCL1 gene could be a target for immunotherapy of B-cell malignancies. We show that TCL1 mRNA and protein are selectively expressed in normal B cells but markedly hyperexpressed in multiple human B-cell lymphomas, including follicular lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, and splenic marginal zone B-cell lymphoma. We demonstrated that TCL1-specific CD8(+) T cells can be generated from HLA-A*0201 (HLA-A2)(+) normal donors and identified TCL1(71-78) (LLPIMWQL) as the minimal epitope recognized by these T cells. More importantly, TCL1(71-78) peptide-specific T cells were present in the peripheral blood and tumor-infiltrating lymphocytes of lymphoma patients, could be expanded in vitro, and lysed autologous tumor cells but not normal B cells in an HLA-A2-restricted manner. Our results suggest that TCL1 is naturally processed and presented on the surface of lymphoma cells for recognition by cytotoxic T cells and can serve as a novel target for development of immunotherapeutic strategies against common B-cell lymphomas.
- Subjects :
- Amino Acid Sequence
Antigens, Neoplasm chemistry
Antigens, Neoplasm genetics
B-Lymphocytes immunology
B-Lymphocytes metabolism
B-Lymphocytes pathology
CD8-Positive T-Lymphocytes immunology
Cell Line, Tumor
Cells, Cultured
Epitopes, T-Lymphocyte chemistry
Epitopes, T-Lymphocyte immunology
Gene Expression Regulation, Neoplastic
HLA-A2 Antigen immunology
Humans
Lymphoma, B-Cell pathology
Proto-Oncogene Proteins chemistry
Proto-Oncogene Proteins genetics
Tumor Cells, Cultured
Antigens, Neoplasm immunology
Immunotherapy methods
Lymphoma, B-Cell immunology
Lymphoma, B-Cell therapy
Proto-Oncogene Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 120
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 22645177
- Full Text :
- https://doi.org/10.1182/blood-2011-09-382838