Division of Hematology and Medical Oncology, Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Curr Med Chem. 2012;19(25):4298-305. doi: 10.2174/092986712802884303.
Monoclonal antibodies (mAbs) have greatly advanced the field of anti-cancer immunotherapy and have made a major impact in clinical medicine. While more mAbs have been approved by the FDA and entered into the clinical therapeutic arena with indications to treat various solid tumors and hematologic malignancies, extensive efforts have also been made to make mAb therapy more effective. Combination therapy of anti-tumor mAbs with chemotherapeutic drugs has been widely used in the clinical patient care. In addition, many immune stimulating agents have been specifically studied for this very purpose. One compound in particular, β-glucan, has shown very promising and exciting results in pre-clinical animal models and early phase human clinical trials. β-Glucans are naturally occurring, abundant polysaccharides with different structures that can be extracted and purified from fungi, bacteria, oats and barley. The active components of yeast-derived β-glucan exert their unique immune stimulating functions by binding specifically to complement receptor 3 (CR3) via lectin-like domain (LLD) and activating CR3 to promote cellular cytotoxicity of iC3b-coated cancer cells. In addition, particulate yeast-derived β-glucan stimulates both innate and adaptive anti-tumor immune responses. This review covers the anti-cancer mechanisms of anti-tumor mAbs and β-glucans, the pre-clinical studies done with β-glucans in conjunction with anti-tumor mAbs in human carcinoma xenograft models, and the preliminary results of human clinical trials with different β-glucans, as well as those of phase I/II and III studies using the combination of yeast-derived soluble β-glucan and anti-tumor mAbs.
单克隆抗体（mAbs）极大地推动了癌症免疫治疗领域的发展，并在临床医学中产生了重大影响。虽然已有更多的 mAbs 通过了 FDA 的批准，并进入临床治疗领域，用于治疗各种实体瘤和血液恶性肿瘤，但人们仍在努力使 mAb 治疗更有效。抗肿瘤 mAbs 与化疗药物的联合治疗已广泛应用于临床患者治疗中。此外，许多免疫刺激剂也为此进行了专门研究。特别是一种化合物β-葡聚糖，在临床前动物模型和早期人体临床试验中显示出非常有希望和令人兴奋的结果。β-葡聚糖是天然存在的、丰富的多糖，具有不同的结构，可以从真菌、细菌、燕麦和大麦中提取和纯化。酵母来源的β-葡聚糖的活性成分通过其凝集素样结构域（LLD）特异性结合补体受体 3（CR3），并激活 CR3 来促进 iC3b 包被的癌细胞的细胞毒性，从而发挥其独特的免疫刺激功能。此外，颗粒状酵母来源的β-葡聚糖刺激先天和适应性抗肿瘤免疫反应。本文综述了抗肿瘤 mAbs 和β-葡聚糖的抗肿瘤机制、β-葡聚糖与抗肿瘤 mAbs 联合用于人类癌移植模型的临床前研究，以及不同β-葡聚糖的人体临床试验初步结果，以及使用酵母来源的可溶性β-葡聚糖和抗肿瘤 mAbs 联合的 I/II 期和 III 期研究的结果。
