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 journalArticle

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
Externally publishedYes

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Cyclin D1
Cytotoxic T-Lymphocytes
Immunotherapy
Neoplasms
Epitopes
HLA-A2 Antigen
T-Lymphocytes
Tissue Donors
Mantle-Cell Lymphoma
Antigen-Presenting Cells
Tumor Cell Line
Colonic Neoplasms
Cell Cycle
B-Lymphocytes
Research Design
Clone Cells
Enzyme-Linked Immunosorbent Assay
Peptides
HLA-A*02:01 antigen

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kondo, E., Maecker, B., Weihrauch, M. R., Wickenhauser, C., Zeng, W., Nadler, L. M., ... Von Bergwelt-Baildon, M. S. (2008). Cyclin D1-specific cytotoxic T lymphocytes are present in the repertoire of cancer patients: Implications for cancer immunotherapy. Clinical Cancer Research, 14(20), 6574-6579. https://doi.org/10.1158/1078-0432.CCR-08-0825

Cyclin D1-specific cytotoxic T lymphocytes are present in the repertoire of cancer patients : Implications for cancer immunotherapy. / Kondo, Eisei; Maecker, Britta; Weihrauch, Martin R.; Wickenhauser, Claudia; Zeng, Wanyong; Nadler, Lee M.; Schultze, Joachim L.; Von Bergwelt-Baildon, Michael S.

In: Clinical Cancer Research, Vol. 14, No. 20, 15.10.2008, p. 6574-6579.

Research output: Contribution to journalArticle

Kondo, E, Maecker, B, Weihrauch, MR, Wickenhauser, C, Zeng, W, Nadler, LM, Schultze, JL & Von Bergwelt-Baildon, MS 2008, 'Cyclin D1-specific cytotoxic T lymphocytes are present in the repertoire of cancer patients: Implications for cancer immunotherapy', Clinical Cancer Research, vol. 14, no. 20, pp. 6574-6579. https://doi.org/10.1158/1078-0432.CCR-08-0825
Kondo, Eisei ; Maecker, Britta ; Weihrauch, Martin R. ; Wickenhauser, Claudia ; Zeng, Wanyong ; Nadler, Lee M. ; Schultze, Joachim L. ; Von Bergwelt-Baildon, Michael S. / Cyclin D1-specific cytotoxic T lymphocytes are present in the repertoire of cancer patients : Implications for cancer immunotherapy. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 20. pp. 6574-6579.
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AU - Wickenhauser, Claudia

AU - Zeng, Wanyong

AU - Nadler, Lee M.

AU - Schultze, Joachim L.

AU - Von Bergwelt-Baildon, Michael S.

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