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特定的山药植物提取物增强 TCL 负载的基于树突细胞的癌症疫苗的效力。

Specific Dioscorea Phytoextracts Enhance Potency of TCL-Loaded DC-Based Cancer Vaccines.

机构信息

Department of Food and Nutrition, Providence University, No. 200, Section 7, Taiwan Boulevard, Shalu District, Taichung 43301, Taiwan ; Institute of Agricultural Biotechnology Research Center, Academia Sinica, No. 128, Section 2, Academia Road, Nankang, Taipei 11529, Taiwan.

出版信息

Evid Based Complement Alternat Med. 2013;2013:932040. doi: 10.1155/2013/932040. Epub 2013 Jul 7.

Abstract

Dioscorea tuber phytoextracts can confer immunomodulatory activities ex vivo and improve regeneration of bone marrow cells in vivo. In present study, we evaluated specific Dioscorea phytoextracts for use ex vivo as a bone-marrow-derived dendritic cell- (DC-) based vaccine adjuvant for cancer immunotherapy. Fractionated Dioscorea extracts (DsII) were assayed for their effect on maturation and functions of DC ex vivo and antimelanoma activity of DC-based vaccine in vivo. The phytoextract from 50-75% ethanol-precipitated fraction of Dioscorea alata var. purpurea Tainung no. 5 tuber, designated as DsII-TN5, showed a strong augmentation of tumor cell lysate- (TCL-) loaded DC-mediated activation of T-cell proliferation. DsII-TN5 stimulated the expression of CD40, CD80, CD86, and IL-1 β in TCL-loaded DCs and downregulated the expression of TGF- β 1. DC vaccines prepared by a specific schema (TCL (2 h) + LPS (22 h)) showed the strongest antitumor activity. DsII-TN5 as a DC vaccine adjuvant showed strong antimelanoma activity and reduced myeloid-derived suppressor cell (MDSC) population in tested mice. DsII-TN5 can also activate DCs to enhance Th1- and Th17-related cytokine expressions. Biochemical analysis showed that DsII-TN5 consists mainly of polysaccharides containing a high level (53%) of mannose residues. We suggest that DsII-TN5 may have potential for future application as a potent, cost-effective adjuvant for DC-based cancer vaccines.

摘要

薯蓣属植物提取物可在体外赋予免疫调节活性,并改善体内骨髓细胞的再生。在本研究中,我们评估了特定的薯蓣属植物提取物,以作为基于骨髓来源树突状细胞(DC)的癌症免疫疗法的疫苗佐剂在体外使用。薯蓣属植物提取物(DsII)的分级提取物用于检测其对 DC 体外成熟和功能的影响,以及基于 DC 的疫苗在体内的抗黑色素瘤活性。从 50-75%乙醇沉淀的大薯(Dioscorea alata var. purpurea Tainung no. 5)薯蓣属植物提取物中分离得到的植物提取物,命名为 DsII-TN5,可强烈增强肿瘤细胞裂解物(TCL)负载的 DC 介导的 T 细胞增殖激活。DsII-TN5 刺激 TCL 负载的 DC 中 CD40、CD80、CD86 和 IL-1β的表达,并下调 TGF-β1 的表达。通过特定方案(TCL(2 h)+ LPS(22 h))制备的 DC 疫苗显示出最强的抗肿瘤活性。作为 DC 疫苗佐剂的 DsII-TN5 显示出强烈的抗黑色素瘤活性,并减少了测试小鼠中的髓样来源抑制细胞(MDSC)群体。DsII-TN5 还可以激活 DC 以增强 Th1 和 Th17 相关细胞因子的表达。生化分析表明,DsII-TN5 主要由含有高水平(53%)甘露糖残基的多糖组成。我们认为 DsII-TN5 可能具有作为基于 DC 的癌症疫苗的有效、经济有效的佐剂的应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d8/3723319/505a4f92b4d6/ECAM2013-932040.001.jpg

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