Successful immunogene therapy using colon cancer cells (colon 26) transfected with plasmid vector containing mature interleukin-18 cDNA and the Igκ leader sequence

Kiyoshi Yoshimura, Shoichi Hazama, Norio Iizuka, Shigefumi Yoshino, Koutaro Yamamoto, Masahiro Muraguchi, Yasuichi Ohmoto, Takafumi Noma, Masaaki Oka

Research output: Contribution to journalArticle

Abstract

IL-18 is a novel cytokine that induces interferon (IFN) -γ secretion and plays an important role in antitumor immunity. In the present study, we constructed plasmid vectors encoding the murine mature IL- 18 cDNA linked with the Igκ leader sequence and the pro-IL-18 cDNA to estimate the efficacy of the mature IL-18 vector and to evaluate IL-18-producing tumor cells as a tumor vaccine. Colon 26 cells were transfected with the abovementioned vectors or with vector alone (mock). Reverse transcription-polymerase chain reaction analysis showed increased expression of murine IL-18 cDNA in both mature IL-18 and pro-IL-18 transfectants in comparison to that in mock transfected cells. The ability of the culture supernatants of mature IL-18 transfectants to induce IFN-γ secretion was extremely high (40-140 pg/106 cells) in comparison to that of pro-IL-18 transfectants (4-18 pg/106 cells). When injected into syngeneic BALB/c mice, the growth of mature IL-18 transfectants, but not pro-IL-18 transfectants, was significantly less than that in mock transfected cells (P+ and anti-CD8+ antibodies. These data suggest that the rejection of mature IL-18/colon 26 cells was mediated through T-cell activation. Gene therapy using mature IL-18 transfectants containing a plasmid vector and the Igκ leader sequence may be a useful tumor vaccine.

Original languageEnglish (US)
Pages (from-to)9-16
Number of pages8
JournalCancer Gene Therapy
Volume8
Issue number1
StatePublished - 2001
Externally publishedYes

Keywords

  • Gene therapy
  • IL-18
  • Immunotherapy
  • Plasmid

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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  • Cite this

    Yoshimura, K., Hazama, S., Iizuka, N., Yoshino, S., Yamamoto, K., Muraguchi, M., Ohmoto, Y., Noma, T., & Oka, M. (2001). Successful immunogene therapy using colon cancer cells (colon 26) transfected with plasmid vector containing mature interleukin-18 cDNA and the Igκ leader sequence. Cancer Gene Therapy, 8(1), 9-16.