Application of a Mathematical Model for Production of Recombinant Antibody 14D9 by Nicotiana tabacum Cell Suspension Batch Culture

Abstract

One of the bottlenecks in biopharming is the scalability and modeling of batch cultures at bench scale, largely because bioreactors and mathematical models were originally designed for microbe cultures. Thus, a mathematical model that acknowledges kinetic and growth processes, basic aspect of cell structure, and physiology and productivity is needed. We proposed to apply a new combination of structured and unstructured mathematical models for plant cell cultivation in a bioreactor.The mathematical model is based on the theory of energy-limited growth that allows precise evaluation of a cell population age structure into the bioreactor. We have scaledthe full antibody r14D9 expressed in N. tabacumcell suspension from a 225 mL-Erlenmeyer flask to 2L-bioreactor and applied the above mentioned mathematical model in order to estimate and predict the growth rate of cell cultures and the accumulation of the recombinant protein. Under the proposed model two inoculum sizes were used in order to obtain experimental data, specific growth rates and productivity, which allow the analysis of the predictions under different conditions.