The shared tumor associated antigen cyclin-A2 is recognized by high-avidity T-cells

Eisei Kondo, Britta Maecker, Andreas Draube, Nela Klein-Gonzalez, Alexander Shimabukuro-Vornhagen, Joachim L. Schultze, Michael S. Von Bergwelt-Baildon

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cyclin-A2, a key cell cycle regulator, has been shown to be overexpressed in various types of malignancies with little expression in normal tissue. Such tumor-associated genes potentially are useful targets for cancer immunotherapy. However, high-avidity cyclin-specific T cells are considered to be thymically deleted. We identified at least one nonameric HLA-A*0201 binding cyclin-A2 epitope by a reverse immunology approach. Using a highly efficient T-cell expansion system that is based on CD40-activated B (CD40-B) cells as sole antigen-presenting cells we successfully generated cyclin-A2 specific CTL from HLA-A*0201+ donors. Interestingly, high-avidity cyclin-A2 specific CTL lines, which recognized peptide-pulsed and antigen expressing target cells, were indeed generated by stimulation with CD40-B cells when pulsed with low concentrations of peptide, whereas CD40-B cells pulsed at saturating concentrations could only induce low-avidity CTL, which recognized peptide-pulsed target cells only. One high-avidity CTL line was subcloned and CTL clones, whose peptide concentration required for half-maximal lysis were less than 1 nM, could lyse cyclin-A2 expressing tumor cells. Taken together, cyclin A2 is an attractive candidate for immune intervention in a significant number of cancer patients and high-avidity T cells can be readily generated using CD40-B cells as antigen-presenting cells.

Original languageEnglish
Pages (from-to)2474-2478
Number of pages5
JournalInternational Journal of Cancer
Volume125
Issue number10
DOIs
Publication statusPublished - Nov 15 2009

Keywords

  • CTL
  • Cyclin-A2
  • Immunotherapy
  • Tumor
  • Tumor antigen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Kondo, E., Maecker, B., Draube, A., Klein-Gonzalez, N., Shimabukuro-Vornhagen, A., Schultze, J. L., & Von Bergwelt-Baildon, M. S. (2009). The shared tumor associated antigen cyclin-A2 is recognized by high-avidity T-cells. International Journal of Cancer, 125(10), 2474-2478. https://doi.org/10.1002/ijc.24629