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评估选定的免疫调节糖蛋白作为癌症免疫治疗辅助手段的效果。

Evaluation of Selected Immunomodulatory Glycoproteins as an Adjunct to Cancer Immunotherapy.

作者信息

Sekhon Bhagwant Kaur, Roubin Rebecca Heidi, Li Yiming, Devi Parimala B, Nammi Srinivas, Fan Kei, Sze Daniel Man-yuen

机构信息

Faculty of Pharmacy, The University of Sydney, New South Wales, 2006, Australia.

School of Medical Science, University of Western Sydney, Campbelltown, New South Wales, 2560, Australia.

出版信息

PLoS One. 2016 Jan 22;11(1):e0146881. doi: 10.1371/journal.pone.0146881. eCollection 2016.

Abstract

Polysaccharopeptide (PSP), from Coriolus versicolor, has been used widely as an adjuvant to chemotherapy with demonstrated anti-tumor and broad immunomodulating effects. While PSP's mechanism of action still remains unknown, its enhanced immunomodulatory potential with acacia gum is of great interest. Acacia gum, which also contains polysaccharides and glycoproteins, has been demonstrated to be immunopotentiating. To elucidate whether PSP directly activates T-cell-dependent B-cell responses in vivo, we used a well-established hapten carrier system (Nitrophenyl-chicken gamma globulin (NP-CGG)). 6-week C57BL/6 male mice were immunised with 50 μg of NP25-CGG alum precipitate intraperitoneally. Mice were gavaged daily with 50 mg/kg PSP in a vehicle containing acacia gum and sacrificed at days 0, 4, 7, 10, 14 and 21. ELISA was used to measure the total and relative hapten-specific anti-NP IgA, IgM and IgG titre levels compared to the controls. It was found that PSP, combined with acacia gum, significantly increased total IgG titre levels at day 4 (P< 0.05), decreased IgM titre levels at days 4 and 21 (P< 0.05) with no alterations observed in the IgA or IgE titre levels at any of the time points measured. Our results suggest that while PSP combined with acacia gum appears to exert weak immunological effects through specific T-cell dependent B-cell responses, they are likely to be broad and non-specific which supports the current literature on PSP. We report for the first time the application of a well-established hapten-carrier system that can be used to characterise and delineate specific T-cell dependent B-cell responses of potential immunomodulatory glycoprotein-based herbal medicines combinations in vivo.

摘要

云芝多糖肽(PSP)提取自云芝,作为化疗辅助药物已被广泛应用,具有抗肿瘤和广泛的免疫调节作用。虽然PSP的作用机制尚不清楚,但其与阿拉伯胶联用增强免疫调节的潜力备受关注。阿拉伯胶也含有多糖和糖蛋白,已被证明具有免疫增强作用。为了阐明PSP在体内是否直接激活T细胞依赖性B细胞反应,我们使用了一个成熟的半抗原载体系统(硝基苯基 - 鸡γ球蛋白(NP - CGG))。将6周龄的C57BL / 6雄性小鼠腹腔注射50μg NP25 - CGG明矾沉淀物进行免疫。小鼠每天灌胃含有阿拉伯胶的载体中的50mg / kg PSP,并在第0、4、7、10、14和21天处死。与对照组相比,采用酶联免疫吸附测定法(ELISA)测量总半抗原特异性抗NP IgA、IgM和IgG滴度水平及相对滴度水平。结果发现,PSP与阿拉伯胶联用在第4天显著提高了总IgG滴度水平(P <0.05),在第4天和第21天降低了IgM滴度水平(P <0.05),在任何测量时间点均未观察到IgA或IgE滴度水平的变化。我们的结果表明,虽然PSP与阿拉伯胶联用似乎通过特定的T细胞依赖性B细胞反应发挥微弱的免疫作用,但它们可能是广泛且非特异性的,这与目前关于PSP的文献一致。我们首次报道了一种成熟的半抗原载体系统的应用,该系统可用于体内表征和描绘潜在的基于免疫调节糖蛋白的草药组合的特定T细胞依赖性B细胞反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5993/4723152/23db8a7d9144/pone.0146881.g001.jpg

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