Combined yeast-derived beta-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.
Liu
Jingjing
J
Tumor Immunobiology Program, James Graham Brown Cancer Center, Louisville, KY 40202, USA.
Gunn
Lacey
L
Hansen
Richard
R
Yan
Jun
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018448:Models, Immunological; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D009504:Neutrophils / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000276:immunology; D012995:Solubility; D014183:Transplantation, Heterologous; D047071:beta-Glucans / Q000008:administration & dosage* / Q000276:immunology / Q000302:isolation & purification
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D047071:beta-Glucans