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

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.

Tumor necrosis factor-alpha production-regulating activity of phthalimide derivatives in genetically modified murine melanoma cells B78H1.

The effect of imides, monothioimides, trimellitimides, as well as 5'-deoxy-5'-phthaloylamino-derivatives of azidothymidine on tumor necrosis factor-alpha (TNF-alpha) production by genetically modified murine B78H1 melanoma cells transduced with the gene for human TNF-alpha (B78/TNF) was investigated. It was found that N-(adamant-1-yl)monothiophthalimide (1e) and N-(adamant-2-yl)-monothiophthalimide (1f) showed over 200% enhancing of TNF-alpha production while some of imides were inhibitors.