Cancer immunotherapy using a polysaccharide from Codium fragile in a murine model.

ABSTRACT

Natural polysaccharides have shown immune modulatory effects with low toxicity in both animal and human models. A previous study has shown that the polysaccharide from Codium fragile (CFP) promotes natural killer (NK) cell activation in mice. Since NK cell activation is mediated by dendritic cells (DCs), we examined the effect of CFP on DC activation and evaluated the subsequent induction of anti-cancer immunity in a murine model. Treatment with CFP induced activation of bone marrow-derived dendritic cells (BMDCs). Moreover, subcutaneous injection of CFP promoted the activation of spleen and lymph node DCs in vivo. CFP also induced activation of DCs in tumor-bearing mice, and combination treatment with CFP and ovalbumin (OVA) promoted OVA-specific T cell activation, which consequently promoted infiltration of IFN-γ-and TNF-α-producing OT-1 and OT-II cells into the tumors. Moreover, combination treatment using CFP and cancer self-antigen efficiently inhibited B16 tumor growth in the mouse model. Treatment with CFP also enhanced anti-PD-L1 antibody mediated anti-cancer immunity in the CT-26 carcinoma-bearing BALB/c mice. Taken together these data suggest that CFP may function as an adjuvant in the treatment of cancer by enhancing immune activation. Abbreviations CFP Codium fragile polysaccharide; NK natural killer; IFN interferon; TNF tumor necrosis factor; IL interleukin; tdLN tumor draining lymph node; BMDC bone marrow-derived dendritic cell; OVA ovalbumin; Ab antibody; Ag antigen; DC dendritic cell; CTL cytotoxic T lymphocyte; APC antigen-presenting cell; pDC plasmacytoid dendritic cell; mDC myeloid dendritic cell; MHC major histocompatibility complex; CR3 complement receptor type 3; TLR Toll-like receptor; LPS lipopolysaccharide; SP sulfated polysaccharide; TRP2 tyrosinase-related protein 2; SR-A scavenger receptor-A.