MODELING MONOCLONAL ANTIBODY PRODUCTION IN NICOTIANA
BENTHAMIANA PLANT CELL SUSPENSION CULTURE
Sara C. Sukenik1 and Karen A. McDonald2
1
Department of Biomedical Engineering, University of California, Davis
2
Department of Chemical Engineering, University of California, Davis
Technologies that enable rapid, large-scale production of novel protein therapeutics or vaccines
will be invaluable in future infectious disease outbreaks. We are developing a novel bioreactorbased production process for ZMapp, an experimental cocktail of monoclonal antibodies used to
treat Ebola. Our system uses genetically engineered Agrobacterium tumefaciens to mediate
transient protein expression in Nicotiana benthamiana plant cell suspension culture. Plant cells are
being explored as an alternative to mammalian expression systems because they can also produce
complex proteins, but provide enhanced safety and efficacy in certain cases. A key advantage of
our system is that Agrobacterium constructs could be produced for use in a manufacturing process
more rapidly than a transgenic plant or animal cell line. We have developed a mathematical model
for this new process which uses differential equations to describe the growth of plant cells, gene
transfer from Agrobacterium to plant cells, and antibody production. Sensitivity analysis has been
performed using the model to determine which parameters in the process are most critical to
experimentally optimize. The model will be further refined as additional experimental data are
obtained to elucidate underlying molecular mechanisms of key process steps. By improving our
understanding of the process, this model could reduce the time and cost of development for novel
proteins produced using our system.