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

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. (C) 2009 Elsevier Inc. All rights reserved.