Combined yeast-derived β-glucan with anti-tumor monoclonal antibody for cancer immunotherapy

Tumor Immunobiology Program, James Graham Brown Cancer Center, Louisville, KY 40202, USA.
Experimental and Molecular Pathology (Impact Factor: 2.71). 07/2009; 86(3):208-14. DOI: 10.1016/j.yexmp.2009.01.006
Source: PubMed


Beta-glucan is an immuno-stimulating agent that has been used to treat cancer and infectious disease for many years with varying and unpredictable efficacy. Recent studies have unraveled the action mode of yeast-derived beta-glucan in combination with anti-tumor monoclonal antibodies (mAbs) in cancer therapy. It has demonstrated that particulate or large molecular weight soluble beta-glucans are ingested and processed by macrophages. These macrophages secrete the active moiety that primes neutrophil complement receptor 3 (CR3) to kill iC3b-opsonized tumor cells. In vitro and in vivo data demonstrate that successful combination therapy requires complement activation and deposition on tumors and CR3 expression on granulocytes. Pre-clinical animal studies have demonstrated the efficacy of combined beta-glucan with anti-tumor mAb therapy in terms of tumor regression and long-term survival. Clinical trials are underway using anti-epidermal growth factor receptor mAb (cetuximab) in combination with beta-glucan for metastatic colorectal cancer. This review provides a brief overview of this combination therapy in cancer and describes in detail the beta-glucan composition and structure, mechanism of action, and preclinical studies in human carcinoma xenograft models. It is proposed that the addition of beta-glucan will further improve the therapeutic efficacy of anti-tumor mAbs in cancer patients.

Download full-text


Available from: Jun Yan,
  • Source
    • "Given their diversity, fungal EPSs could be used in medicine , for example as antioxidant and antimicrobial agents applied for acceleration of wound healing and fighting bacterial and viral infections as well as antitumor agents activating immune response in the host and supporting chemotherapy treatment (Zhang et al. 2002, 2007; Chen and Seviour 2007; Liu et al. 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Fungal polysaccharides (PSs) are the subject of research in many fields of science and industry. Many properties of PSs have already been confirmed and the list of postulated functions continues to grow. Fungal PSs are classified into different groups according to systematic affinity, structure (linear and branched), sugar composition (homo- and heteropolysaccharides), type of bonds between the monomers (β-(1 → 3), β-(1 → 6), and α-(1 → 3)) and their location in the cell (cell wall PSs, exoPSs, and endoPSs). Exopolysaccharides (EPSs) are most frequently studied fungal PSs but their definition, classification, and origin are still not clear and should be explained. Ascomycota and Basidiomycota fungi producing EPS have different ecological positions (saprotrophic and endophytic, pathogenic or symbiotic-mycorrhizae fungi); therefore, EPSs play different biological functions, for example in the protection against environmental stress factors and in interactions with other organisms. EPSs obtained from Ascomycota and Basidiomycota fungal cultures are known for their antioxidant, immunostimulating, antitumor, and antimicrobial properties. The major objective of the presented review article was to provide a detailed description of the state-of-the-art knowledge of the effectiveness of EPS production by filamentous and yeast Ascomycota and Basidiomycota fungi and techniques of derivation of EPSs, their biochemical characteristics, and biological properties allowing comprehensive analysis as well as indication of similarities and differences between these fungal groups. Understanding the role of EPSs in a variety of processes and their application in food or pharmaceutical industries requires improvement of the techniques of their derivation, purification, and characterization. The detailed analyses of data concerning the derivation and application of Ascomycota and Basidiomycota EPSs can facilitate development and trace the direction of application of these EPSs in different branches of industry, agriculture, and medicine.
    World Journal of Microbiology and Biotechnology (Formerly MIRCEN Journal of Applied Microbiology and Biotechnology) 09/2015; DOI:10.1007/s11274-015-1937-8 · 1.78 Impact Factor
  • Source
    • "As GSP-2 is highly water-soluble, we suppose that it might share some similar characters with the well studied yeast water-soluble beta-glucan (PGG), which could be identified by the toll-like receptor-4 on the surface of the cells. The influence of the structural factors such as the length of the backbone, degree of polymerization, degree of branching and the length of the side chain to the interaction between this fraction and the toll-like receptors deserve further studies [40]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A polysaccharide named GSP-2 with a molecular size of 32 kDa was isolated from the fruiting bodies of Ganoderma sinense. Its structure was well elucidated, by a combined utilization of chemical and spectroscopic techniques, to be a β-glucan with a backbone of (1→4)- and (1→6)-Glcp, bearing terminal- and (1→3)-Glcp side-chains at O-3 position of (1→6)-Glcp. Immunological assay exhibited that GSP-2 significantly induced the proliferation of BALB/c mice splenocytes with target on only B cells, and enhanced the production of several cytokines in human peripheral blood mononuclear cells and derived dendritic cells. Besides, the fluorescent labeled GSP-2 was phagocytosed by the RAW 264.7 cells and induced the nitric oxide secretion from the cells.
    PLoS ONE 07/2014; 9(7):e100380. DOI:10.1371/journal.pone.0100380 · 3.23 Impact Factor
  • Source
    • "BioMed Research International of í µí»½-glucans on immune cells is the interaction of these polysaccharides with the CR3 receptors [7] [8]. Besides their action on immune cells, í µí»½-glucans also inhibit angiogenesis by cutting off the supply of nutrients to tumor cells and, in consequence, inhibiting their development [9]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A new exopolysaccharide preparation isolated from stationary cultures of the white rot fungus Ganoderma applanatum (GpEPS) was tested in terms of its bioactive properties including its cytotoxic and immunostimulatory effect. The results indicate that the tested GpEPS (at concentrations above 22.85 µg/mL and 228.5 µg/mL) may exhibit selective activity against tumor cells (cell lines SiHa) and stimulate production of TNF-α THP-1-derived macrophages at the level of 752.17 pg/mL. The GpEPS showed antibacterial properties against Staphyloccoccus aureus and a toxic effect against Vibrio fischeri cells (82.8% cell damage). High cholesterol-binding capacity and triglycerides-binding capacity (57.9% and 41.6% after 24 h of incubation with the tested substances, resp.) were also detected for the investigated samples of GpEPS.
    BioMed Research International 07/2014; 2014(1). DOI:10.1155/2014/743812 · 1.58 Impact Factor
Show more