A novel adjuvant Ling Zhi-8 enhances the efficacy of DNA cancer vaccine by activating dendritic cells

Chi Chen Lin, Yen Ling Yu, Chia Chiao Shih, Ko Jiunn Liu, Keng Liang Ou, Ling Zong Hong, Jody D.C. Chen, Ching Liang Chu

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43 Citations (Scopus)

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 p185neu 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.

Original languageEnglish
Pages (from-to)1019-1027
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume60
Issue number7
DOIs
Publication statusPublished - 2011

Keywords

  • Adjuvant
  • Cancer therapy
  • Dendritic cell
  • DNA vaccine
  • TLR4

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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  • Cite this

    Lin, C. C., Yu, Y. L., Shih, C. C., Liu, K. J., Ou, K. L., Hong, L. Z., Chen, J. D. C., & Chu, C. L. (2011). A novel adjuvant Ling Zhi-8 enhances the efficacy of DNA cancer vaccine by activating dendritic cells. Cancer Immunology, Immunotherapy, 60(7), 1019-1027. https://doi.org/10.1007/s00262-011-1016-4