Open Access

Identification of a novel HLA-A*02:01-restricted cytotoxic T lymphocyte epitope derived from the EML4-ALK fusion gene

  • Authors:
    • Mayuko Yoshimura
    • Yoshitaka Tada
    • Kazuya Ofuzi
    • Masakazu Yamamoto
    • Tetsuya Nakatsura
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  • Published online on: May 19, 2014     https://doi.org/10.3892/or.2014.3198
  • Pages: 33-39
  • Copyright: © Yoshimura et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

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.
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July-2014
Volume 32 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yoshimura M, Tada Y, Ofuzi K, Yamamoto M and Nakatsura T: Identification of a novel HLA-A*02:01-restricted cytotoxic T lymphocyte epitope derived from the EML4-ALK fusion gene. Oncol Rep 32: 33-39, 2014.
APA
Yoshimura, M., Tada, Y., Ofuzi, K., Yamamoto, M., & Nakatsura, T. (2014). Identification of a novel HLA-A*02:01-restricted cytotoxic T lymphocyte epitope derived from the EML4-ALK fusion gene. Oncology Reports, 32, 33-39. https://doi.org/10.3892/or.2014.3198
MLA
Yoshimura, M., Tada, Y., Ofuzi, K., Yamamoto, M., Nakatsura, T."Identification of a novel HLA-A*02:01-restricted cytotoxic T lymphocyte epitope derived from the EML4-ALK fusion gene". Oncology Reports 32.1 (2014): 33-39.
Chicago
Yoshimura, M., Tada, Y., Ofuzi, K., Yamamoto, M., Nakatsura, T."Identification of a novel HLA-A*02:01-restricted cytotoxic T lymphocyte epitope derived from the EML4-ALK fusion gene". Oncology Reports 32, no. 1 (2014): 33-39. https://doi.org/10.3892/or.2014.3198