A purified acidic polysaccharide from Sarcandra glabra as vaccine adjuvant to enhance anti-tumor effect of cancer vaccine

Carbohydr Polym. 2021 Jul 1:263:117967. doi: 10.1016/j.carbpol.2021.117967. Epub 2021 Mar 19.

Abstract

Immunological adjuvants are an important part of tumor vaccines and are critical for stimulating anti-tumor immune responses. However, the clinical needs of strong adjuvants have not been met. In this work, we found that the purified acidic polysaccharide from Sarcandra glabra, named p-SGP, is an ideal adjuvant for tumor vaccines. Cancer vaccines could induce stronger humoral and cellular immune responses when they are adjuvanted with p-SGP. Compared with CpG, a well-studied adjuvant, p-SGP significantly augmented the anti-tumor immunity of various cancer vaccines, which is leading to noticeable inhibition of tumor growth and metastasis in tumor-bearing mice. Moreover, p-SGP promoted dendritic cells (DCs) maturation and Th1-polarized immune response. Toll-like receptor 4 (TLR4) inhibitor TAK-242 could significantly inhibit the expression of mature molecules on the surface of DCs stimulated by p-SGP, suggesting that p-SGP could play the role of activating DCs through the TLR4 receptor. Results of RNA-seq showed that the Delta-like ligand 4 (DLL4) gene in the pathway Th1 and Th2 cell differentiation was significantly up-regulated in the DCs treated with p-SGP, suggesting that p-SGP has a unique mechanism of enhancing anti-tumor immunity.

Keywords: Adjuvant; Cancer vaccine; Immune response; Natural polysaccharide; Sarcandra glabra.

MeSH terms

  • Acids / chemistry
  • Adaptor Proteins, Signal Transducing / genetics
  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Calcium-Binding Proteins / genetics
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / pharmacology*
  • Cell Line, Tumor
  • Dendritic Cells / immunology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Immunity, Cellular / drug effects
  • Immunity, Humoral / drug effects
  • Magnoliopsida / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Polysaccharides / administration & dosage
  • Polysaccharides / chemistry
  • Polysaccharides / immunology*
  • Th1 Cells / immunology
  • Toll-Like Receptor 4 / metabolism
  • Up-Regulation

Substances

  • Acids
  • Adaptor Proteins, Signal Transducing
  • Adjuvants, Immunologic
  • Calcium-Binding Proteins
  • Cancer Vaccines
  • DLL4 protein, mouse
  • Polysaccharides
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4