Autophagy-inducing peptide increases CHO cell monoclonal antibody production in batch and fed-batch cultures
| Autor: | Marko Kryworuchko, Katrin Braasch, James M. Piret |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0106 biological sciences
Bioengineering Peptide CHO Cells 01 natural sciences Applied Microbiology and Biotechnology Hydrolysate law.invention 03 medical and health sciences Bioreactors Cricetulus law 010608 biotechnology Cricetinae Protein biosynthesis Autophagy Animals Humans Bioprocess 030304 developmental biology chemistry.chemical_classification 0303 health sciences Chemistry Chinese hamster ovary cell Recombinant Proteins Cell biology Culture Media Batch Cell Culture Techniques Immunoglobulin G Recombinant DNA Peptides Flux (metabolism) Biotechnology |
| Zdroj: | Biotechnology and bioengineeringREFERENCES. 118(5) |
| ISSN: | 1097-0290 |
| Popis: | The development of generic biopharmaceuticals is increasing the pressures for enhanced bioprocess productivity and yields. Autophagy ("self-eating") is a cellular process that allows cells to mitigate stresses such as nutrient deprivation. Reputed autophagy inhibitors have also been shown to increase autophagic flux under certain conditions, and enhance recombinant protein productivity in Chinese Hamster Ovary (CHO) cultures. Since peptides are commonly added to bioprocess culture media in hydrolysates, we evaluated the impact on productivity of an autophagy-inducing peptide (AIP), derived from the cellular autophagy protein Beclin 1. This was analyzed in CHO cell batch and fed-batch serum-free cultures producing a human Immunoglobulin G1 (IgG1). Interestingly, the addition of 1-4 µM AIP enhanced productivity in a concentration-dependent manner. Cell-specific productivity increased up to 1.8-fold in batch cultures, while in fed-batch cultures a maximum twofold increase in IgG concentration was observed. An initial drop in cell viability also occurred before cultures recovered normal growth. Overall, these findings strongly support the value of investigating the effects of autophagy pathway modulation, and in particular, the use of this AIP medium additive to increase CHO cell biotherapeutic protein production and yields. |
| Databáze: | OpenAIRE |
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