Open Access

A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model

  • Authors:
    • Kosuke Higashi
    • Shoichi Hazama
    • Atsuhiro Araki
    • Kiyoshi Yoshimura
    • Norio Iizuka
    • Shigefumi Yoshino
    • Takafumi Noma
    • Masaaki Oka
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  • Published online on: July 22, 2014     https://doi.org/10.3892/ijo.2014.2557
  • Pages: 1412-1420
  • Copyright: © Higashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

A therapeutic vaccine against minimal residual cancer cells is needed for the treatment of patients with colorectal cancer. Several gene therapy studies have revealed that the combination of a suicide gene and cytokine gene might induce effective antitumor immunity. In this study, we constructed an interleukin (IL)-18 and herpes simplex virus-thymidine kinase (HSV-TK) expression vector driven by the human telomerase reverse transcriptase (hTERT) promoter to study the efficacy of combination gene therapy with IL-18 and the HSV-TK suicide gene. Low immunogenic colon 26 cells were used for transfection and inoculation into syngeneic BALB/c mice. Large established tumors of colon 26 transfectants expressing IL-18 and HSV-TK driven by the hTERT promoter were completely eradicated after GCV administration in syngeneic BALB/c mice. Immunohistochemical analysis at the tumor rejection sites revealed enormous infiltrations of CD8+ T lymphocytes as well as CD4+ T lymphocytes and CD11b+ monocytes. Moreover, established distant tumors were completely eradicated by vaccination with the IL-18 and HSV-TK transfectants in combination with GCV. These data suggest that the IL-18 and suicide gene therapy can elicit antitumor specific immunity. In conclusion, gene therapy with IL-18 and HSV-TK plasmid vector driven by the hTERT promoter may be useful for cancer vaccination.
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October 2014
Volume 45 Issue 4

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

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Copy and paste a formatted citation
APA
Higashi, K., Hazama, S., Araki, A., Yoshimura, K., Iizuka, N., Yoshino, S. ... Oka, M. (2014). A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model. International Journal of Oncology, 45, 1412-1420. https://doi.org/10.3892/ijo.2014.2557
MLA
Higashi, K., Hazama, S., Araki, A., Yoshimura, K., Iizuka, N., Yoshino, S., Noma, T., Oka, M."A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model". International Journal of Oncology 45.4 (2014): 1412-1420.
Chicago
Higashi, K., Hazama, S., Araki, A., Yoshimura, K., Iizuka, N., Yoshino, S., Noma, T., Oka, M."A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model". International Journal of Oncology 45, no. 4 (2014): 1412-1420. https://doi.org/10.3892/ijo.2014.2557