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
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- Citations32
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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.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=3042628507&origin=inward; http://dx.doi.org/10.1158/1078-0432.ccr-04-0022; http://www.ncbi.nlm.nih.gov/pubmed/15217954; https://aacrjournals.org/clincancerres/article/10/12/4165/182213/CpG-Immunostimulatory-Oligodeoxynucleotide-1826; http://clincancerres.aacrjournals.org/cgi/doi/10.1158/1078-0432.CCR-04-0022; https://syndication.highwire.org/content/doi/10.1158/1078-0432.CCR-04-0022; https://dx.doi.org/10.1158/1078-0432.ccr-04-0022; https://clincancerres.aacrjournals.org/content/10/12/4165
American Association for Cancer Research (AACR)
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