Liu Jingjing, Gunn Lacey, Hansen Richard, Yan Jun
Tumor Immunobiology Program, James Graham Brown Cancer Center, Louisville, KY 40202, USA.
Exp Mol Pathol. 2009 Jun;86(3):208-14. doi: 10.1016/j.yexmp.2009.01.006. Epub 2009 Jan 21.
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.
β-葡聚糖是一种免疫刺激剂，多年来一直用于治疗癌症和传染病，但其疗效各异且难以预测。最近的研究揭示了酵母来源的β-葡聚糖在癌症治疗中与抗肿瘤单克隆抗体（mAb）联合使用的作用模式。已证明颗粒状或大分子量可溶性β-葡聚糖可被巨噬细胞摄取和处理。这些巨噬细胞分泌活性部分，该活性部分可激活中性粒细胞补体受体3（CR3）以杀死被iC3b调理的肿瘤细胞。体外和体内数据表明，成功的联合治疗需要补体激活并沉积在肿瘤上以及粒细胞上表达CR3。临床前动物研究已证明联合β-葡聚糖与抗肿瘤mAb治疗在肿瘤消退和长期生存方面的疗效。目前正在进行使用抗表皮生长因子受体mAb（西妥昔单抗）联合β-葡聚糖治疗转移性结直肠癌的临床试验。本综述简要概述了这种癌症联合治疗方法，并详细描述了β-葡聚糖的组成和结构、作用机制以及在人癌异种移植模型中的临床前研究。有人提出，添加β-葡聚糖将进一步提高抗肿瘤mAb对癌症患者的治疗效果。
