A novel adjuvant Ling Zhi-8 enhances the efficacy of DNA cancer vaccine by activating dendritic cells |
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Authors: | 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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Institution: | (1) Institute of Biomedical Sciences, National Chung Hsin University, Taichung, Taiwan;(2) Department of Medical Education and Research, Taichung Veteran General Hospital, Taichung, Taiwan;(3) Vaccine Research and Development Center, National Health Research Institutes, Miaoli, Taiwan;(4) National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan;(5) Research Center for Biomedical Implants and Microsurgery Devices, Taipei Medical University, Taipei, Taiwan;(6) Yeastern Biotech Co., 6F, No 23, Lane 169, Kang-Ning St., Shijr Area, New Taipei City 221, Taiwan |
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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. |
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