The boosting effect of co-transduction with cytokine genes on cancer vaccine therapy using genetically modified dendritic cells expressing tumor-associated antigen

  • Authors: Toshiyasu Ojima, Makoto Iwahashi, Masaki Nakamura, Kenji Matsuda, Teiji Naka, Mikihito Nakamori, Kentaro Ueda, Koichiro Ishida, Hiroki Yamaue
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  • Published online on: Saturday, April 1, 2006
  • Pages: 947-953
  • DOI: 10.3892/ijo.28.4.947

Abstract

The T-helper 1 (Th1) immune reaction is most important in dendritic cell (DC)-based immunotherapy. Interleukin 12 (IL-12) and granulocyte macrophage colony-stimulating factor (GM-CSF) play a pivotal role in inducing Th1 and cytotoxic T lymphocyte (CTL) responses. In this study, DCs expressing the natural tumor antigen gp70 of BALB/c-derived CT26 were adenovirally transduced with the IL-12 gene and/or GM-CSF gene, and it was examined whether vaccinations using these genetically engineered DCs can induce strong therapeutic antitumor immunity. Mice were immunized once by subcutaneous (s.c.) injection with genetically modified DCs. The cytotoxic activity of splenocytes against CT26 was assayed in a 51Cr-release assay 14 days after immunization. The therapeutic efficacy of the vaccination was examined in s.c. tumor models. The cytotoxic activity of CTLs against CT26 in mice immunized with DCs expressing gp70 (DC-AxCAgp70) was significantly augmented by co-transduction with the GM-CSF/IL-12 gene (p<0.0001) and remarkably reduced by the depletion of CD4+ or CD8+ cells (p<0.01). The cytotoxic activity against CT26 of the plain spleen cells in mice immunized with DC-AxCAgp70/GM-CSF/IL-12 was significantly higher than that in mice immunized with DC-AxCAgp70 (p<0.0001), and this activity decreased to almost 50% upon the depletion of NK cells. Vaccinations using DC-AxCAgp70/GM-CSF/IL-12 or DC-AxCAgp70/IL-12 could elicit potent therapeutic immunity in s.c. tumor models; tumor-free mice were observed in these vaccination groups. However, there was no significant difference between these two groups. A vaccination therapy using DCs co-transduced with the TAA gene and Th 1-type cytokine genes, especially the IL-12 gene, is ideal for immunotherapy in terms of the activation of DCs, NK cells, CD4+ T cells and CD8+ T cells, and may be useful in the clinical application of a cancer vaccine therapy.
Journal Cover

April 2006
Volume 28 Issue 4

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

2012 Impact Factor: 2.657
Ranked #31/196 Oncology
(total number of cites)

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APA
Ojima, T., Iwahashi, M., Nakamura, M., Matsuda, K., Naka, T., Nakamori, M., Ueda, K., Ishida, K., & Yamaue, H. (2006). The boosting effect of co-transduction with cytokine genes on cancer vaccine therapy using genetically modified dendritic cells expressing tumor-associated antigen. International Journal of Oncology, 28(4), 947-953.
MLA
Ojima, Iwahashi, Nakamura, Matsuda, Naka, Nakamori, Ueda, Ishida, and Hiroki Yamaue. "The boosting effect of co-transduction with cytokine genes on cancer vaccine therapy using genetically modified dendritic cells expressing tumor-associated antigen." International Journal of Oncology International Journal of Oncology 28.4 (2006): 947-953.
Chicago
Ojima, Iwahashi, Nakamura, Matsuda, Naka, Nakamori, Ueda, Ishida, and Hiroki Yamaue. "The boosting effect of co-transduction with cytokine genes on cancer vaccine therapy using genetically modified dendritic cells expressing tumor-associated antigen." International Journal of Oncology International Journal of Oncology 28 no. 4 (2006): 947-953.