title: Immunotoxicity assessment of rice-derived recombinant human serum albumin using human peripheral blood mononuclear cells.
abstract: 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 the 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-γ), tumor necrosis factor-alpha (TNF-α), 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.
authors.affiliation: State Key Laboratory of Hybrid Rice and College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Hybrid Rice and College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Hybrid Rice and College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Hybrid Rice and College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Analysis and Testing center, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Immunology, College of Basic Medical Science, Wuhan University, Wuhan, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Ruan
authors.affiliation: Department of Immunology, College of Basic Medical Science, Wuhan University, Wuhan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Immunology, College of Basic Medical Science, Wuhan University, Wuhan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Immunology, College of Basic Medical Science, Wuhan University, Wuhan, China.
authors.forename: Ruijing
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Department of Immunology, College of Basic Medical Science, Wuhan University, Wuhan, China.
authors.forename: Shengwu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Immunology, College of Basic Medical Science, Wuhan University, Wuhan, China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Hybrid Rice and College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Daichang
authors.initials: D
authors.lastname: Yang
mesh_terms: D016207:Cytokines / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D012275:Oryza; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology; D012709:Serum Albumin / Q000009:adverse effects* / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; D012709:Serum Albumin
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