Orally administered β-glucans enhance anti-tumor effects of monoclonal antibodies
Orally administered β-glucans enhance anti-tumor effects of monoclonal antibodies
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DOI：
10.1007/s00262-002-0321-3
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发表时间：
2002-11-01
影响因子：
5.8
通讯作者：
Knuckles, B
中科院分区：
文献类型：
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作者：
Cheung, NKV;Modak, S;Knuckles, B
β-葡聚糖引发白细胞CR 3以增强细胞毒性，并与抗肿瘤单克隆抗体（mAb）协同作用。我们使用免疫缺陷异种移植肿瘤模型研究了易得的（1->3）-β-D-葡聚糖，并检查了其抗肿瘤作用与理化性质的关系。建立皮下（s.c.）通过胃内注射每天口服β-葡聚糖和静脉内（i. v.）每周两次。对照小鼠接受单独的mAb或单独的β-葡聚糖。随时间监测肿瘤大小。通过糖键分析和高效分子排阻色谱结合多角度激光散射检测对β-葡聚糖进行了研究。口服β-D-葡聚糖大大增强了mAb对小鼠体内已形成肿瘤的抗肿瘤作用。我们观察到这种β-葡聚糖效应与抗原（GD 2、GD 3、CD 20、表皮生长因子受体）无关。HER-2）、人肿瘤类型（神经母细胞瘤、黑素瘤。淋巴瘤、表皮样癌和乳腺癌）或肿瘤部位（s.c.相对于系统性）。这种效应与口服（1-->3），（1-->4）-β-D-葡聚糖的分子大小有关（1-->3）。(1-->6）-β-D-葡聚糖也与mAb协同作用，尽管效果通常不太明显。鉴于口服β-D-葡聚糖治疗的良好疗效和毒性特征，含有β-葡聚糖的天然产品在癌症治疗中作为单克隆抗体治疗效果增强剂的作用值得进一步研究。
beta-Glucan primes leukocyte CR3 for enhanced cytotoxicity and synergizes with anti-tumor monoclonal antibodies (mAb). We studied readily available (1-->3)-beta-D-glucan using the immune deficient xenograft tumor models, and examined the relationship of its anti-tumor effect and physico-chemical properties. Established subcutaneous (s.c.) human xenografts were treated for 29 days orally with daily beta-glucan by intragastric injection and mAb intravenously (i.v.) twice weekly. Control mice received either mAb alone or beta-glucan alone. Tumor sizes were monitored over time. beta-Glucans were studied by carbohydrate linkage analysis, and high performance size-exclusion chromatography with multiple angle laser scattering detection. Orally administered beta-D-glucan greatly enhanced the anti-tumor effects of mAb against established tumors in mice. We observed this beta-glucan effect irrespective of antigen (GD2, GD3, CD20, epidermal growth factor-receptor. HER-2), human tumor type (neuroblastoma, melanoma. lymphoma, epidermoid carcinoma and breast carcinoma) or tumor sites (s.c. versus systemic). This effect correlated with the molecular size of the (1-->3),(1-->4)-beta-D-glucan, Orally administered (1-->3).(1-->6)-beta-D-glucans also synergized with mAb., although the effect was generally less marked. Given the favorable efficacy and toxicity profile of oral beta-D-glucan treatment, the role of natural products that contain beta-glucan in cancer treatment as an enhancer of the effect of mAb therapy deserves further study.