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

Oncoimmunology. 2020 Jun 1;9(1):1772663. doi: 10.1080/2162402X.2020.1772663.

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.

Keywords: Codium fragile polysaccharide; adjuvant; anti-cancer; cytotoxic T lymphocyte; dendritic cell; helper T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • China
  • Disease Models, Animal
  • Immunotherapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms* / drug therapy
  • Polysaccharides / pharmacology

Substances

  • Polysaccharides

Grant support

This work was supported by the National Research Foundation of Korea under Grant numbers [NRF-2019R1C1C1003334 and NRF-2018R1A6A1A03023584] and the 13th Five-Year National Major Science and Technology Project on Discovery of New Drugs: Construction of Technology Platform for Clinical Evaluation on Anti-HIV Drugs [2017ZX09304027].