Immunotoxicity Assessment of Rice-Derived Recombinant Human Serum Albumin Using Human Peripheral Blood Mononuclear Cells
Immunotoxicity Assessment of Rice-Derived Recombinant Human Serum Albumin Using Human Peripheral Blood Mononuclear Cells
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DOI：
10.1371/journal.pone.0104426
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发表时间：
2014-08-06
期刊：
影响因子：
3.7
通讯作者：
Yang, Daichang
中科院分区：
文献类型：
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作者：
Fu, Kai;Cheng, Qin;Yang, Daichang
人血清白蛋白（HSA）在临床上广泛用于治疗各种疾病，如低蛋白血症、失血性休克、严重烧伤、血小板减少性腹水和胎儿成红细胞增多症。为了解决供应短缺和有限的人类供体的高安全风险，我们最近开发了重组技术，从水稻胚乳中生产HSA。为了在首次人体试验（FIH）之前评估来自水稻的HSA（OsrHSA）的潜在风险，我们比较了OsrHSA和血浆来源的HSA（pHSA），使用人外周血单核细胞（PBMC）评估了免疫反应和毒性的可能性。结果表明，OsrHSA和pHSA在1x和5x剂量下均不刺激T细胞增殖。我们还发现OsrHSA和pHSA处理的细胞之间的CD 4（+）和CD 8（+）T细胞亚群的分布没有显著差异。此外，结果显示，OsrHSA和pHSA之间在细胞因子如干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-10和IL-4的产生方面没有显著差异。我们的结果表明，OsrHSA具有等效的免疫毒性pHSA时，使用PBMC模型。此外，这种离体系统可以提供一种替代方法来预测新的生物药物开发中的潜在风险。
Human serum albumin (HSA) is extensively used in clinics to treat a variety of diseases, such as hypoproteinemia, hemorrhagic shock, serious burn injuries, cirrhotic ascites and fetal erythroblastosis. To address supply shortages and high safety risks from limited human donors, we recently developed recombinant technology to produce HSA from rice endosperm. To assess he risk potential of HSA derived from Oryza sativa (OsrHSA) before a First-in-human (FIH) trial, we compared OsrHSA and plasma-derived HSA (pHSA), evaluating the potential for an immune reaction and toxicity using human peripheral blood mononuclear cells (PBMCs). The results indicated that neither OsrHSA nor pHSA stimulated T cell proliferation at 1x and 5x dosages. We also found no significant differences in the profiles of the CD4(+) and CD8(+) T cell subsets between OsrHSA- and pHSA-treated cells. Furthermore, the results showed that there were no significant differences between OsrHSA and pHSA in the production of cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-10 and IL-4. Our results demonstrated that OsrHSA has equivalent immunotoxicity to pHSA when using the PBMC model. Moreover, this ex vivo system could provide an alternative approach to predict potential risks in novel biopharmaceutical development.