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

Abstract

β-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 β-glucan in combination with anti-tumor monoclonal antibodies (mAbs) in cancer therapy. It has demonstrated that particulate or large molecular weight soluble β-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 β-glucan with anti-tumor mAbs therapy in terms of tumor regression and long-term survival. Clinical trials are underway using anti-epidermal growth factor receptor mAb (Erbitux) in combination with β-glucan for metastatic colorectal cancer. This review provides a brief overview of this combination therapy in cancer and describes in detail the β-glucan composition and structure, mechanism of action, and preclinical studies in human carcinoma xenograft models. It is proposed that the addition of β-glucan will further improve the therapeutic efficacy of anti-tumor mAbs in cancer patients.

Potentiating Effect of .BETA.-Glucans on Photodynamic Therapy of Implanted Cancer Cells in Mice

“…We recently found that high molecular weight, unbranched (1 3),(1 4)-β -glucan from barley suppresses growth of PDT-treated Lewis lung carcinoma tumors (Akramiene et al 2009), but others reported that also schizophyllan, a branched high molecular weight (1 3),(1 6)-β -glucan, potentiates PDT (Krosl and Korbelik 1994). These studies agree with recent observations that apart from the presence of the (1 3),(1 6)-β linkage, the size and complexity of β -glucan are important for the interaction with human cells (Liu et al 2009). Therefore, β -glucan from different sources may affect tumor growth differently.…”

“…Without β -glucan, iC3b-opsonized tumor cells are resistant to killing, because they, like all human and mammalian cells, lack β -glucan in their membrane. Microbes can activate the lectin domain on CR3, leading to effective phagocytosis and cytotoxic degranulation (Cheung and Modak 2002;Gelderman et al 2004;Liu et al 2009). Therefore, these processes can be induced by coadministration of β -glucan together with the agents, which cause opsonization of tumor cells by iC3b fragment.…”

“…Oat and barley β -glucans are linear polymers with (1 3)-β and (1 4)-β -linkages in their backbone, but no branches; mushroom and fungal β -glucans have the (1 3)-β -linkage in the backbone and (1 6)-β -linked branches (Cheung and Modak 2002;Brown and Gordon 2003;Liu et al 2009). It was previously thought that (1 3),(1 6)-β linkage was required for the antitumor effect of β -glucans (Bohn and BeMiller 1995), but later it was shown that (1 3),(1 4)-β -glucan binds CR3, activates antibody-dependent cellular cytotoxicity in vitro, and acts in synergy with monoclonal antibodies in vivo (Cheung and Modak 2002).…”

Particulate β-glucan regulates the immunosuppression of granulocytic myeloid-derived suppressor cells by inhibiting NFIA expression

“…30 Furthermore, it has been recently reported b-glucans enhance Ag-specific T cells and B cells responses by promoting the maturation and antigen presentation of DCs. 12,[16][17][18]31 Thus, b-glucans play a key role in the innate and adaptive immune responses.…”

A Study of Saccharomyces cerevisiae Cell Wall Glucans

“…In recent years, there has been increasing biotechnological and commercial interest in yeast cell wall components, including their use as biological response modifiers, anti-cancer agents, bioadsorbents, ingredients in food processing and cosmetic formulations, and as systems for immobilizing oral vaccines, antibodies and enzymes of industrial significance 6,25,33 . This increase in interest has occurred concomitantly with our better understanding of the chemical composition, genetic regulation and functional properties of cell wall components.…”