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Article Open Access

Large-scale expansion of γδ T cells and peptide-specific cytotoxic T cells using zoledronate for adoptive immunotherapy

  • Authors:
    • Toshiaki Yoshikawa
    • Masashi Takahara
    • Mai Tomiyama
    • Mie Nieda
    • Ryuji Maekawa
    • Tetsuya Nakatsura
  • View Affiliations / Copyright

    Affiliations: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa 277-8577, Japan, Medinet Medical Institute, Setagaya-ku, Tokyo 158-0096, Japan
    Copyright: © Yoshikawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1847-1856
    |
    Published online on: September 3, 2014
       https://doi.org/10.3892/ijo.2014.2634
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Abstract

Specific cellular immunotherapy for cancer requires efficient generation and expansion of cytotoxic T lymphocytes (CTLs) that recognize tumor-associated antigens. However, it is difficult to isolate and expand functionally active T-cells ex vivo. In this study, we investigated the efficacy of a new method to induce expansion of antigen-specific CTLs for adoptive immunotherapy. We used tumor-associated antigen glypican-3 (GPC3)-derived peptide and cytomegalovirus (CMV)-derived peptide as antigens. Treatment of human peripheral blood mononuclear cells (PBMCs) with zoledronate is a method that enables large-scale γδ T-cell expansion. To induce expansion of γδ T cells and antigen-specific CTLs, the PBMCs of healthy volunteers or patients vaccinated with GPC3 peptide were cultured with both peptide and zoledronate for 14 days. The expansion of γδ T cells and peptide-specific CTLs from a few PBMCs using zoledronate yields cell numbers sufficient for adoptive transfer. The rate of increase of GPC3‑specific CTLs was approximately 24- to 170,000-fold. These CD8+ cells, including CTLs, showed GPC3-specific cytotoxicity against SK-Hep-1/hGPC3 and T2 pulsed with GPC3 peptide, but not against SK-Hep-1/vec and T2 pulsed with human immunodeficiency virus peptide. On the other hand, CD8- cells, including γδ T cells, showed cytotoxicity against SK-Hep-1/hGPC3 and SK-Hep-1/vec, but did not show GPC3 specificity. Furthermore, adoptive cell transfer of CD8+ cells, CD8- cells, and total cells after expansion significantly inhibited tumor growth in an NOD/SCID mouse model. This study indicates that simultaneous expansion of γδ T cells and peptide-specific CTLs using zoledronate is useful for adoptive immunotherapy.
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Copy and paste a formatted citation
Spandidos Publications style
Yoshikawa T, Takahara M, Tomiyama M, Nieda M, Maekawa R and Nakatsura T: Large-scale expansion of γδ T cells and peptide-specific cytotoxic T cells using zoledronate for adoptive immunotherapy. Int J Oncol 45: 1847-1856, 2014.
APA
Yoshikawa, T., Takahara, M., Tomiyama, M., Nieda, M., Maekawa, R., & Nakatsura, T. (2014). Large-scale expansion of γδ T cells and peptide-specific cytotoxic T cells using zoledronate for adoptive immunotherapy. International Journal of Oncology, 45, 1847-1856. https://doi.org/10.3892/ijo.2014.2634
MLA
Yoshikawa, T., Takahara, M., Tomiyama, M., Nieda, M., Maekawa, R., Nakatsura, T."Large-scale expansion of γδ T cells and peptide-specific cytotoxic T cells using zoledronate for adoptive immunotherapy". International Journal of Oncology 45.5 (2014): 1847-1856.
Chicago
Yoshikawa, T., Takahara, M., Tomiyama, M., Nieda, M., Maekawa, R., Nakatsura, T."Large-scale expansion of γδ T cells and peptide-specific cytotoxic T cells using zoledronate for adoptive immunotherapy". International Journal of Oncology 45, no. 5 (2014): 1847-1856. https://doi.org/10.3892/ijo.2014.2634
Copy and paste a formatted citation
x
Spandidos Publications style
Yoshikawa T, Takahara M, Tomiyama M, Nieda M, Maekawa R and Nakatsura T: Large-scale expansion of γδ T cells and peptide-specific cytotoxic T cells using zoledronate for adoptive immunotherapy. Int J Oncol 45: 1847-1856, 2014.
APA
Yoshikawa, T., Takahara, M., Tomiyama, M., Nieda, M., Maekawa, R., & Nakatsura, T. (2014). Large-scale expansion of γδ T cells and peptide-specific cytotoxic T cells using zoledronate for adoptive immunotherapy. International Journal of Oncology, 45, 1847-1856. https://doi.org/10.3892/ijo.2014.2634
MLA
Yoshikawa, T., Takahara, M., Tomiyama, M., Nieda, M., Maekawa, R., Nakatsura, T."Large-scale expansion of γδ T cells and peptide-specific cytotoxic T cells using zoledronate for adoptive immunotherapy". International Journal of Oncology 45.5 (2014): 1847-1856.
Chicago
Yoshikawa, T., Takahara, M., Tomiyama, M., Nieda, M., Maekawa, R., Nakatsura, T."Large-scale expansion of γδ T cells and peptide-specific cytotoxic T cells using zoledronate for adoptive immunotherapy". International Journal of Oncology 45, no. 5 (2014): 1847-1856. https://doi.org/10.3892/ijo.2014.2634
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