A research team led by Prof. Daichang Yang, from College of Life Sciences, Wuhan University, and Wuhan  Healthgen Biotechnology Co., Ltd. started the research and development of using plant-derived therapeutic proteins to replace the plasma-derived ones since 2006, has achieved a breakthrough in the technology and completed the preclinical studies of plant-derived recombinant human serum albumin. The technology filled the vacancy in this field in China. This paper entitled “Immunotoxicity Assessment of Rice-Derived Recombinant Human Serum Albumin Using Human Peripheral Blood Mononuclear Cells” has been published on line in the journal Proceedings of the Public Library of Science (PLoS ONE) on 6th August 2014.

To assess the risk potential of HSA derived from Oryza sativa (OsrHSA) before a First-in-human (FIH) trial, this study 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. The study 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.

PLoS ONE’s reviewer gave a high evaluation to this article: “The manuscript addresses the very challenging topic of predicting immunogenicity of a biologic. Ultimately, humans are the best model for testing immunogenicity of recombinant human albumin versus plasma-derived HSA. ”

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, and also used in cell culture applications. To address supply shortages and high safety risks from limited human donors, Healthgen Biotech developed recombinant technology to produce HSA from rice endosperm, has achieved the recombinant HSA scale-up manufacture and industrialization. Now the product has been completed the preclinical studies, and accomplished the key step towards human use medicine.