Characterization of BAX inhibitor-1 as a novel leukemia-associated antigen
| Autor: | K von Schwarzenberg, Stefanie Ae Held, Peter Brossart, Anita Bringmann, Frank Grünebach, Susanne M. Schmidt, Tobias A W Holderried, T König, Annkristin Heine, Stefan Stevanovic |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Epitopes T-Lymphocyte HLA-A24 Antigen chemical and pharmacologic phenomena Enzyme-Linked Immunosorbent Assay Epitope Antigen Antigens Neoplasm hemic and lymphatic diseases Tumor Cells Cultured Medicine Cytotoxic T cell Humans RNA Neoplasm Antigen-presenting cell Cell Proliferation Membrane Glycoproteins HLA-A Antigens business.industry HLA-A24 Myeloid leukemia Membrane Proteins hemic and immune systems Hematology Dendritic cell Dendritic Cells Molecular biology Peptide Fragments Leukemia Myeloid Acute Oncology business RNA transfection Apoptosis Regulatory Proteins Blast Crisis T-Lymphocytes Cytotoxic |
| Zdroj: | Leukemia. 23(10) |
| ISSN: | 1476-5551 |
| Popis: | Using dendritic cells (DCs) electroporated with whole RNA isolated from blasts of a patient with acute myeloid leukemia (AML), we were able to generate leukemia-specific cytotoxic T lymphocytes (CTLs) capable of recognizing the leucemic cells. To identify T-cell epitopes mediating lysis of malignant cells, peptides were eluted from the patient's blasts and analyzed by mass spectrometry (LC/MS)-based peptide sequencing. Using this approach, an HLA-A24-binding peptide derived from Bax inhibitor-1 (BI-1), a regulator of apoptosis pathways, was identified as an epitope recognized by the generated CTLs. To further characterize this novel antigenic peptide, CTLs were induced using DCs electroporated with RNA coding for BI-1 or pulsed with the cognate peptide. These CTLs generated from healthy donors in vitro efficiently lysed the patient's blasts as well as other HLA-matched leukemic cells. In conclusion, we identified a BI-1 peptide as a novel immunogenic tumor-associated antigen (TAA) in AML. In vitro induction of BI-1-specific CTLs by RNA transfection or pulsing of DCs with the synthetically generated peptide was a feasible and highly effective method to generate leukemia-specific CTLs. As BI-1 is (over-) expressed in a broad variety of malignancies, it may represent an interesting novel TAA in the context of cancer vaccines. |
| Databáze: | OpenAIRE |
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