Cyclin D1-specific cytotoxic T lymphocytes are present in the repertoire of cancer patients: Implications for cancer immunotherapy

Eisei Kondo, Britta Maecker, Martin R. Weihrauch, Claudia Wickenhauser, Wanyong Zeng, Lee M. Nadler, Joachim L. Schultze, Michael S. Von Bergwelt-Baildon

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Purpose: Cyclin D1, a key cell cycle regulator, is overexpressed in multiple types of cancer. Such tumor-associated genes may be useful targets for cancer immunotherapy. Nevertheless, it had previously been suggested that efficient T cells recognizing cyclin D1-derived epitopes are absent from the repertoire because of thymic deletion. We attempted to induce autologous CTLfrom healthy donors and patients with cyclin D1-overexpressing tumors using a highly efficient T-cell expansion system based on CD40-activated B cells as antigen-presenting cells. Experimental Design: Cyclin D1-derived, HLA-A*0201-restricted epitopes were predicted by multiple computer algorithms, screened in HLA-A2-binding assays, and used forT-cell stimulation. The generated CTL lines and clones were analyzed by IFN-γ enzyme-linked immunosorbent spot assay or cytolysis assay. Results: After screening, at least two naturally processed and presented HLA-A*0201-binding cyclin D1 epitopes were identified. CTL specific for these epitopes could be successfully generated from HLA-A2 + donors. T cells efficiently recognized target cells pulsed with the cognate peptide and cyclin D1-expressing tumor cell lines in an HLA-A*0201-restricted manner. More importantly, HLA-A*0201- matched, primary cyclin D1 + tumor cells were efficiently recognized by cyclin D1-specific CTL. These CTL could be generated from patients with mantle cell lymphoma and cyclin D1 + colon cancer. Conclusions: These results underscore that cyclin D1 needs to be considered as a target for broad-based antitumor immunotherapy.

Original languageEnglish
Pages (from-to)6574-6579
Number of pages6
JournalClinical Cancer Research
Volume14
Issue number20
DOIs
Publication statusPublished - Oct 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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