PlumX Metrics
Embed PlumX Metrics

CpG immunostimulatory oligodeoxynucleotide 1826 enhances antitumor effect of interleukin 12 gene-modified tumor vaccine in a melanoma model in mice

Clinical Cancer Research, ISSN: 1078-0432, Vol: 10, Issue: 12 I, Page: 4165-4175
2004
  • 32
    Citations
  • 0
    Usage
  • 27
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

Purpose: The effectiveness of interleukin (IL)-12-secreting tumor vaccines in the treatment of mouse tumors could be enhanced by concurrent application of cytokines and costimulatory molecules. We investigated the therapeutic potential of IL-12 gene-transduced melanoma vaccine in combination with CpG immunostimulatory oligodeoxynucleotide (ODN) 1826, an adjuvant known to favor development of Th1-biased immune response, in a B78-H1 (B78) melanoma model in mice. Experimental Design: Mice injected with B78 melanoma cells were treated with irradiated IL-12 gene-transduced B78 cells [B78/IL-12(X)] and/or ODN 1826. Mechanisms responsible for the antitumor effects of the treatment were investigated using fluorescence-activated cell sorter analysis, a standard Cr releasing assay, 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assay, and ELISA. Results: Single injection of B78/IL-12(X) cells had no effect on tumor growth, whereas seven consecutive daily injections of ODN 1826 markedly inhibited tumor progression with occasional curative effects. When used in combination, B78/IL-12(X) cells and ODN 1826 caused additional tumor growth reduction and eradication of tumors in 62% of treated mice. The combined treatment activated local inflammatory response against tumor but also induced systemic antitumor immunity. In vitro studies have shown that when used together, B78/IL-12(X) cells and ODN 1826 induced a potent Th1 response and suggested the role of IFN-γ in activation of the host immune response. The antitumor effects in double-treated mice were accompanied by the development of cytotoxic effectors in the spleen and activation of macrophages. Conclusions: The results provided the evidence that the combination of IL-12 gene-modified melanoma vaccine and ODN 1826 induces synergistically systemic and local antitumor immunity.

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know