Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells

  • Authors:
    • Toshiyasu Ojima
    • Makoto Iwahashi
    • Masaki Nakamura
    • Kenji Matsuda
    • Mikihito Nakamori
    • Kentaro Ueda
    • Teiji Naka
    • Masahiro Katsuda
    • Motoki Miyazawa
    • Hiroki Yamaue
  • View Affiliations

  • Published online on: October 1, 2007     https://doi.org/10.3892/ijo.31.4.931
  • Pages: 931-939
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Abstract

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined. A cytotoxic assay using peripheral blood mononuclear cell (PBMC)-derived cytotoxic T lymphocytes (CTLs) was performed in a 4-h 51Cr release assay. The apoptosis of DCs was examined by TdT-mediated dUTP-FITC nick end labeling (TUNEL) assay. CEA-specific CTLs were generated from PBMCs stimulated with genetically modified DCs expressing CEA. The cytotoxicity of these CTLs was augmented by co-transduction of DCs with the GM-CSF gene. Co-transduction of the GM-CSF gene into DCs inhibited apoptosis of these DCs themselves via up-regulation of Bcl-xL expression, leading to the extension of the lifespan of these DCs. Furthermore, the transduction of the GM-CSF gene into DCs also suppressed the incidence of apoptosis of DCs induced by transforming growth factor-β1 (TGFβ-1). Immunotherapy using these genetically modified DCs may therefore be useful with several advantages as follows: i) adenoviral toxicity to DCs can be reduced; ii) the lifespan of vaccinated DCs can be prolonged; and iii) GM-CSF may protect DCs from apoptosis induced by tumor-derived TGFβ-1 in the regional lymph nodes.

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October 2007
Volume 31 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ojima T, Iwahashi M, Nakamura M, Matsuda K, Nakamori M, Ueda K, Naka T, Katsuda M, Miyazawa M, Yamaue H, Yamaue H, et al: Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells. Int J Oncol 31: 931-939, 2007.
APA
Ojima, T., Iwahashi, M., Nakamura, M., Matsuda, K., Nakamori, M., Ueda, K. ... Yamaue, H. (2007). Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells. International Journal of Oncology, 31, 931-939. https://doi.org/10.3892/ijo.31.4.931
MLA
Ojima, T., Iwahashi, M., Nakamura, M., Matsuda, K., Nakamori, M., Ueda, K., Naka, T., Katsuda, M., Miyazawa, M., Yamaue, H."Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells". International Journal of Oncology 31.4 (2007): 931-939.
Chicago
Ojima, T., Iwahashi, M., Nakamura, M., Matsuda, K., Nakamori, M., Ueda, K., Naka, T., Katsuda, M., Miyazawa, M., Yamaue, H."Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells". International Journal of Oncology 31, no. 4 (2007): 931-939. https://doi.org/10.3892/ijo.31.4.931