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 Citations (Scopus)

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

Fingerprint

Aurora Kinase A
Helper-Inducer T-Lymphocytes
Neoplasms
T-Lymphocyte Epitopes
Clone Cells
T-Lymphocytes
Antigens
Immunotherapy
Peptides
Protein-Serine-Threonine Kinases
Neoplasm Antigens
Urinary Bladder Neoplasms
Cell Cycle
Alleles

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

Cite this

Characterization of human CD4 helper T cell responses against Aurora kinase A. / Kobayashi, Hiroya; Azumi, Makoto; Hayashi, Satoshi; Sato, Keisuke; Aoki, Naoko; Kimura, Shoji; Kakizaki, Hidehiro; Nagato, Toshihiro; Harabuchi, Yasuaki; Tateno, Masatoshi; Celis, Esteban.

In: Cancer Immunology, Immunotherapy, Vol. 59, No. 7, 01.07.2010, p. 1029-1039.

Research output: Contribution to journalArticle

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, vol. 59, no. 7, pp. 1029-1039. https://doi.org/10.1007/s00262-010-0826-0
Kobayashi, Hiroya ; Azumi, Makoto ; Hayashi, Satoshi ; Sato, Keisuke ; Aoki, Naoko ; Kimura, Shoji ; Kakizaki, Hidehiro ; Nagato, Toshihiro ; Harabuchi, Yasuaki ; Tateno, Masatoshi ; Celis, Esteban. / Characterization of human CD4 helper T cell responses against Aurora kinase A. In: Cancer Immunology, Immunotherapy. 2010 ; Vol. 59, No. 7. pp. 1029-1039.
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