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.
Highlights
Plant-made pharmaceuticals (PMPs) are a category of therapeutic products based on a plant platform that has developed rapidly over the past two decades [1]
Increased cell apoptosis was observed with OsrHSA, plasma-derived HSA (pHSA) and phosphate-buffered saline (PBS) treatments compared with PHA treatment (Fig. 2)
Abundant cell apoptosis was observed with OsrHSA treatment at a 1x dosage after 72 h compared to pHSA
Summary
Plant-made pharmaceuticals (PMPs) are a category of therapeutic products based on a plant platform that has developed rapidly over the past two decades [1]. Plant cells have successfully been used to produce at least 108 pharmaceuticals; more than 30 PMP products have been evaluated in clinical trials, and nine have been approved for market [2]. Attempts to produce rHSA in various expression systems have been made, including Escherichia coli [9], Saccharomyces cerevisiae [10], Kluyveromyces lactis [11], Pichia pastoris [12], transgenic animals [13], and transgenic plants [6,14,15,16,17]. RHSA has been successfully expressed in these systems, only a few rHSA have proceeded to clinical trials
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