Florian Maria Wurm

Biography

Florian Wurm received his academic training as a Biologist and Molecular Geneticist at the University of Giessen. He joined the Hoechst AG (Behringwerke) in Marburg as head of a laboratory in Virology. Working with immortalized mammalian cells for the establishment of production processes for alpha-interferons provided the first opportunity to combine basic research with medical application. In 1984 he joined Harvard Medical School in Boston as a Research Fellow in Molecular Biology. 1986 he took an offer from Genentech Inc. in San Francisco to work in Process Sciences on the development of large scale manufacturing processes for recombinant proteins. There he has held a number of leading positions and has acquired intimate knowledge in the generation of protein pharmaceuticals in mammalian cells in bioreactors (a number of which are now marketed products). In 1995 he joined the EPFL as a Professor for Biotechnology. Wurm has published more than 250 scientific papers and holds more than 20 patents/patent-applications. His H-index stands at 60 in 2021. He was Chairman (2005-2009) and is member of the Executive Board of the European Society of Animal Cell Technology (ESACT). He serves as a consultant to the pharmaceutical Biotech Industry, mainly in the fields of animal cell technology for recombinant protein production and in regulatory affairs. He works as a scientific reviewer and editior/asscciate editor for a number of international journals in the Biotech field. F.M. Wurm teaches classes to pre- and postgraduate students in the fields of Molecular and Cellular Biotechnology. He was founder and Chief Scientific Officer of ExcellGene SA, a 2001 established company in Monthey, Switzerland. He took the position of President and CEO of ExcellGene in 2015. He retired from the CEO position in 2017 and continues to be President and Chief Scientific Officer of ExcellGene. In 2008 Dr. Wurm was appointed Visiting Professor for Biotechnology at Jinan University in Guangzhou, China. He retired from his position at the EPFL in 2015. His laboratory is closed. With his team at ExcellGene and in collaboration with Dr. Paco Pino, Director of R&D, he continues to explore manufacturing sciences with animal cells in bioreactors.

Official source

https://people.epfl.ch/florian.wurm

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For the treatment of severe COVID-19, supplementation with human plasma-purified alpha-1 antitrypsin (AAT) to patients is currently considered. AAT inhibits host proteases that facilitate viral entry and possesses broad anti-inflammatory and immunomodulatory activities. Researchers have demonstrated that an interaction between SARS-CoV-2 spike protein (S) and lipopolysaccharides (LPS) enhances pro-inflammatory responses in vitro and in vivo. Hence, we wanted to understand the potential anti-inflammatory activities of plasma-derived and recombinant AAT (recAAT) in a model of human total peripheral blood mononuclear cells (PBMCs) exposed to a combination of CHO expressed trimeric spike protein and LPS, ex vivo. We confirmed that cytokine production was enhanced in PBMCs within six hours when low levels of LPS were combined with purified spike proteins ("spike"). In the presence of 0.5 mg/mL recAAT, however, LPS/spike-induced TNF-alpha and IL-1 beta mRNA expression and protein release were significantly inhibited (by about 46-50%) relative to LPS/spike alone. Although without statistical significance, recAAT also reduced production of IL-6 and IL-8. Notably, under the same experimental conditions, the plasma-derived AAT preparation Respreeza (used in native and oxidized forms) did not show significant effects. Our findings imply that an early pro-inflammatory activation of human PBMCs is better controlled by the recombinant version of AAT than the human plasma-derived AAT used here. Considering the increasing clinical interest in AAT therapy as useful to ameliorate the hyper-inflammation seen during COVID-19 infection, different AAT preparations require careful evaluation.

MDPI2021

For the manufacturing of complex biopharmaceuticals using bioreactors with cultivated mammalian cells, high product concentration is an important objective. The phenotype of the cells in a reactor plays an important role. Are clonal cell populations showing high cell-specific growth rates more favorable than cell lines with higher cell-specific productivities or vice versa? Five clonal Chinese hamster ovary cell populations were analyzed based on the data of a 3-month-stability study. We adapted a mechanistic cell culture model to the experimental data of one such clonally derived cell population. Uncertainties and prior knowledge concerning model parameters were considered using Bayesian parameter estimations. This model was used then to define an inoculum train protocol. Based on this, we subsequently simulated the impacts of differences in growth rates (+/- 10%) and production rates (+/- 10% and +/- 50%) on the overall cultivation time, including making the inoculum train cultures; the final production phase, the volumetric titer in that bioreactor and the ratio of both, defined as overall process productivity. We showed thus unequivocally that growth rates have a higher impact (up to three times) on overall process productivity and for product output per year, whereas cells with higher productivity can potentially generate higher product concentrations in the production vessel.

MDPI2021

Naming CHO cells for bio-manufacturing: Genome plasticity and variant phenotypes of cell populations in bioreactors question the relevance of old names

Florian Maria Wurm

Chinese Hamster Ovary [CHO] cells are the workhorse for production of modern biopharmaceuticals. They are however immortalized cells with a high propensity for genetic change. Judging from published culture records, CHO cell populations have undergone hundreds of population doublings since their origin in the late 1950s. Different cell populations were established and named from 1 to 3 decades after their generation, such as CHO-Pro-, CHO-K1, CHO-DG44, CHO-S, CHO-DUK, CHO-DXB-11 to indicate origin and certain phenotypic features. These names are commonly used in scientific publications still today. This article discusses the relevance of such names. We argue that they provide a false sense of identity. To substantiate this, we provide the long (and poorly recorded) history of CHO cells as well as their highly complex genetics. Finally, we suggest an alternative naming system for CHO cells which provides more relevant information. While the implementation of a new naming convention will require substantial discussions among members of the relevant community, it should improve interpretation and comparability between laboratories. This, in turn will help scientific communities and industrial users to attain and further the full potential of CHO cells.

2021