Identification of a novel HLA-A 02:01-restricted cytotoxic T lymphocyte epitope derived from the EML4-ALK fusion gene
| Autor: | Kazuya Ofuzi, Masakazu Yamamoto, Yoshitaka Tada, Tetsuya Nakatsura, Mayuko Yoshimura |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
EML4/ALK Fusion Gene Lung Neoplasms Oncogene Proteins Fusion medicine.drug_class medicine.medical_treatment Epitopes T-Lymphocyte HLA-A24 Antigen EML4-ALK Biology Monoclonal antibody Epitope Cancer immunotherapy Antigen Glypicans Antigens Neoplasm hemic and lymphatic diseases Cell Line Tumor HLA-A2 Antigen CTL clone medicine Tumor Cells Cultured peptide vaccine Cytotoxic T cell Humans General Medicine Immunotherapy Articles Molecular biology CTL lung cancer Oncology Peptides T-Lymphocytes Cytotoxic |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 |
| Popis: | Cancer immunotherapy is a promising new approach to cancer treatment. It has been demonstrated that a high number of tumor-specific cytotoxic T cells (CTLs) is associated with increased disease-specific survival in lung cancer patients. Identification of superior CTL epitopes from tumor antigens is essential for the development of immunotherapy for malignant tumors. The EML4-ALK fusion gene was recently identified in a subset of non-small cell lung cancers (NSCLCs). In this study we searched for HLA-A 02:01- and HLA-A 24:02‑restricted epitopes derived from EML4-ALK by screening predicted EML4-ALK‑derived candidate peptides for the induction of tumor‑reactive CTLs. Nine EML4-ALK‑derived peptides were selected by a computer algorithm based on a permissive HLA-A 02:01 or HLA-A 24:02 binding motif. One of the nine peptides induced peptide-specific CTLs from human peripheral blood mononuclear cells. We were able to generate a peptide‑specific CTL clone. This CTL clone specifically recognized peptide‑pulsed T2 cells and H2228 cells expressing HLA-A 02:01 and EML4-ALK that had been treated with IFN-γ 48 h prior to examination. CTL activity was inhibited by an anti-HLA‑class I monoclonal antibody (W6/32), consistent with a class I-restricted mechanism of cytotoxicity. These results suggest that this peptide (RLSALESRV) is a novel HLA-A 02:01-restricted CTL epitope and that it may be a new target for antigen-specific immunotherapy against EML4‑ALK-positive cancers. |
| Databáze: | OpenAIRE |
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