Combination of the toll like receptor agonist and α-Galactosylceramide as an efficient adjuvant for cancer vaccine

BACKGROUND: DNA vaccines have emerged as an attractive approach for the generation of cytotoxic T lymphocytes (CTL). In our previous study, we found That Toll like receptor (TLR) ligands are promising candidates for the development of novel adjuvants for DNA vaccine. To improve the efficacy of DNA vaccine directed against human papillomavirus (HPV) tumors, we evaluated whether co-administration of a TLR4 ligand, monophosphoryl lipid A (MPL), and Natural Killer T Cell Ligand α-Galactosylceramide(α-GalCer) adjuvants with DNA vaccine would influence the anti-tumor efficacy of DNA vaccinations. METHODS: We investigated the effectiveness of α-GalCer and MPL combination as an adjuvant with an HPV-16 E7 DNA vaccine to enhance antitumor immune responses. RESULTS: By using adjuvant combination for a DNA vaccine, we found that the levels of lymphocyte proliferation, CTL activity, IFN- γ, IL-4 and IL-12 responses, and tumor protection against TC-1 cells were significantly increased compared to the DNA vaccine with individual adjuvants. In addition, inhibition of IL-18 signaling during vaccination decreased IFN-γ responses and tumor protection, and that this inhibition suggested stimulatory role of IL-18 in adjuvant effects of α-GalCer and MPL combination. CONCLUSION: The strong adjuvanticity associated with α-GalCer/MPL combination may to be an important tool in the development of novel and strong cancer immunotherapy.