Ascophyllan functions as an adjuvant to promote anti-cancer effect by dendritic cell activation

// Wei Zhang 1 , Takasi Okimura 2 , Li Xu 1 , Lijun Zhang 1 , Tatsuya Oda 3 , Minseok Kwak 4 , Qing Yu 5,6 and Jun-O Jin 1 1 Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, China 2 Research and Development Division, Hayashikane Sangyo Co., Ltd., Shimonoseki, Yamaguchi, Japan 3 Graduate School of Science and Technology, Nagasaki University, Nagasaki, Japan 4 Department of Chemistry, Pukyong National University, Busan, South Korea 5 Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, MA, USA 6 Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA Correspondence: Jun-O Jin, email: // Keywords : ascophyllan; adjuvant; dendritic cell maturation; cytotoxic lymphocyte activation; anti- cancer; Immunologyand Microbiology Section; Immune response; Immunity Received : August 24, 2015 Accepted : March 11, 2016 Published : March 19, 2016 Abstract Our previous study demonstrated that ascophyllan, a sulfated polysaccharide purified from brown alga, has immune-activating effects. In this study, we evaluated ascophyllan as an adjuvant for its therapeutic and preventive effect on tumor in a mouse melanoma model. Ascophyllan induced migration of DCs to spleen and tumor-draining lymph node (drLN) in a mouse B16 melanoma model. Moreover, ascophyllan induced activation of dendritic cells (DCs), and promoted IFN-γ- and TNF-α-producing Th1 immune responses in tumor-bearing mice. In addition, treatment with a combination of ascophyllan and ovalbumin (OVA) in the tumor-bearing mice promoted proliferation of OVA-specific CD4 and CD8 T cells and migration of those cells into the tumor, consequently inhibiting the tumor growth. Immunization with the combination of ascophyllan and OVA caused enhanced OVA-specific antibody production and memory T cellresponses compared to OVA immunization alone, and almost completely prevented B16-OVA tumor growth upon subsequent tumor challenge. Finally, the combination of ascophyllan and OVA prevented B16-OVA tumor invasion and metastasis into the liver. Thus, these results demonstrate that ascophyllan can function as an adjuvant to induce DC activation, antigen specific CTL activation, Th1 immune response and antibody production, and hence may be useful as a therapeutic and preventive tumor vaccine.