Immunotoxicity assessment of rice-derived recombinant human serum albumin using human peripheral blood mononuclear cells

• Published in: PloS one 2014-08, Vol.9 (8), p.e104426
• Main Authors: Fu, Kai, Cheng, Qin, Liu, Zhenwei, Chen, Zhen, Wang, Yan, Ruan, Honggang, Zhou, Lu, Xiong, Jie, Xiao, Ruijing, Liu, Shengwu, Zhang, Qiuping, Yang, Daichang
• Format: Article
• Language: English
• Subjects: Albumin; Apoptosis; Archives & records; Ascites; Biological response modifiers; Biology and Life Sciences; Biopharmaceuticals; Blood; CD4 antigen; CD8 antigen; Cell growth; Cell proliferation; Clinical trials; Comparative analysis; Cytokines; Cytokines - metabolism; Drug Evaluation, Preclinical; Endosperm; Fetuses; Growth factors; Hemorrhage; Human serum albumin; Humans; Immunoglobulins; Immunology; Immunotoxicity; Interferon; Interleukin; Interleukin 4; Kinases; Laboratories; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Life sciences; Lipids; Liver cirrhosis; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Oryza; Oryza sativa; Peripheral blood mononuclear cells; Pharmaceuticals; Proteins; Recombinant Proteins - adverse effects; Recombinant Proteins - pharmacology; Risk assessment; Risk factors; Saccharomyces cerevisiae; Serum albumin; Serum Albumin - adverse effects; Serum Albumin - pharmacology; Shortages; T cells; Toxicity; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vaccines; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0104426

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.