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High mobility group box 1 ( HMGB 1) is a member of the family of damage‐associated molecular patterns, which cause inflammation and trigger innate immunity through Toll‐like receptors 2/4 and the receptor for advanced glycation end products. We examined the effect of glycyrrhizin, a selective inhibitor of  HMGB 1, on the induction of  CTL s in mice. B6 mice, either  OT ‐1 spleen cell‐transferred or untransferred, were immunized with an s.c. injection of  OVA  257–264  peptide with topical imiquimod, and glycyrrhizin was mixed with the antigen peptide. Proliferation of  OT ‐1 cells after immunization was enhanced by glycyrrhizin. The effect of glycyrrhizin was confirmed in other adjuvant systems, such as CpG oligonucleotide and monophosphoryl lipid A, but glycyrrhizin was not effective in Freund's incomplete adjuvant system. The augmenting effects of glycyrrhizin were also observed in other synthetic  HMGB 1 inhibitors, gabexate mesilate, nafamostat, and sivelestat. Thus, the effects are common to the  HMGB 1 inhibitors. Induction of  CTL s detected by γ‐interferon enzyme‐linked immunospot assay was similarly augmented by glycyrrhizin. In a therapeutic vaccine model, glycyrrhizin inhibited the growth of s.c. transplanted  EG .7 tumors. Expression of inflammatory cytokines in the skin inoculation site was downregulated by glycyrrhizin. These results suggest that  HMGB 1 inhibitors might be useful as a co‐adjuvant for peptide vaccination with an innate immunity receptor‐related adjuvant.

Blockade of high mobility group box 1 augments antitumor T ‐cell response induced by peptide vaccination as a co‐adjuvant