Characterization of human CD4 helper T cell responses against Aurora kinase A

Hiroya Kobayashi, Makoto Azumi, Satoshi Hayashi, Keisuke Sato, Naoko Aoki, Shoji Kimura, Hidehiro Kakizaki, Toshihiro Nagato, Yasuaki Harabuchi, Masatoshi Tateno, Esteban Celis

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Aurora kinase A (Aurora-A) is a cell cycle-associated serine-threonine kinase that is overexpressed by various types of cancer and is highly associated with poor prognosis. Since the expression of Aurora-A in normal tissues has been shown to be significantly lower as compared to tumor cells, this protein is being considered as a potential tumor-associated antigen for developing immunotherapies. The goal in the present study was to identify CD4 helper T lymphocyte (HTL) epitopes for Aurora-A for the design of T cell-based immunotherapies against Aurora-A-expressing tumors. Synthetic peptides corresponding to potential HTL epitopes were identified from Aurora-A and used to stimulate CD4 T lymphocytes in vitro to generate antigen-specific HTL clones that were evaluated for antigen specificity, MHC restriction and for their ability to interact with Aurora-A-expressing tumor cells. The results show that two peptides (Aurora-A161-175 and Aurora-A233-247) were effective in generating HTL responses that were restricted by more than one MHC class II allele (i.e., promiscuous responses). The CD4 HTL clones were able to directly recognize Aurora-A-expressing tumor cells in an antigen-specific and MHC class II-restricted manner and some of the clones displayed cytolytic activity toward Aurora-A + tumor cells. Both of these peptides were capable of stimulating in vitro T cell responses in patients with bladder cancer.

Original languageEnglish (US)
Pages (from-to)1029-1039
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume59
Issue number7
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

Keywords

  • Aurora kinase A
  • CD4 helper T lymphocytes
  • Immunotherapy
  • Major histocompatibility complex class II
  • Tumor antigens

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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    Kobayashi, H., Azumi, M., Hayashi, S., Sato, K., Aoki, N., Kimura, S., Kakizaki, H., Nagato, T., Harabuchi, Y., Tateno, M., & Celis, E. (2010). Characterization of human CD4 helper T cell responses against Aurora kinase A. Cancer Immunology, Immunotherapy, 59(7), 1029-1039. https://doi.org/10.1007/s00262-010-0826-0