title: A novel adjuvant Ling Zhi-8 enhances the efficacy of DNA cancer vaccine by activating dendritic cells.
abstract: DNA vaccine has been suggested to use in cancer therapy, but the efficacy remains to be improved. The immunostimulatory effect of a fungal immunomodulatory protein Ling Zhi-8 (LZ-8) isolated from Ganoderma lucidum has been reported. In this study, we tested the adjuvanticity of LZ-8 for HER-2/neu DNA vaccine against p185(neu) expressing tumor MBT-2 in mice. We found that recombinant LZ-8 stimulated mouse bone marrow-derived dendritic cells (DCs) via TLR4 and its stimulatory effect was not due to any microbe contaminant. In addition, LZ-8 enhanced the ability of DCs to induce antigen-specific T cell activation in vitro and in a subunit vaccine model in vivo. Surprisingly, LZ-8 cotreatment strongly improved the therapeutic effect of DNA vaccine against MBT-2 tumor in mice. This increase in antitumor activity was attributed to the enhancement of vaccine-induced Th1 and CTL responses. Consistent with the results from DCs, the promoting effect of LZ-8 on DNA vaccine was diminished when the MBT-2 tumor cells were grown in TLR4 mutant mice. Thus, we concluded that LZ-8 may be a promising adjuvant to enhance the efficacy of DNA vaccine by activating DCs via TLR4.
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsin University, Taichung, Taiwan. lincc@dragon.nchu.edu.tw
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Lin
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Yu
authors.forename: Chia-Chiao
authors.initials: CC
authors.lastname: Shih
authors.forename: Ko-Jiunn
authors.initials: KJ
authors.lastname: Liu
authors.forename: Keng-Liang
authors.initials: KL
authors.lastname: Ou
authors.forename: Ling-Zong
authors.initials: LZ
authors.lastname: Hong
authors.forename: Jody D C
authors.initials: JD
authors.lastname: Chen
authors.forename: Ching-Liang
authors.initials: CL
authors.lastname: Chu
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D005656:Fungal Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA; C061148:LZ-8 protein, Ganoderma lucidum