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

Kosuke Higashi, Shoichi Hazama, Atsuhiro Araki, Kiyoshi Yoshimura, Norio Iizuka, Shigefumi Yoshino, Takafumi Noma, Masaki Oka

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1412-1420
Number of pages9
JournalInternational Journal of Oncology
Volume45
Issue number4
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Colorectal cancer
  • HSV-TK
  • hTERT promoter
  • Interleukin-18
  • Minimal residual tumor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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