Autophagy‐inducing peptide increases CHO cell monoclonal antibody production in batch and fed‐batch cultures. Issue 5 (19th February 2021)

• Record Type: Journal Article
• Authors: Braasch, Katrin; Kryworuchko, Marko; Piret, James M.
• Is Part Of: Biotechnology and bioengineering. Volume 118:Issue 5(2021)
• Page Start: 1876
• Page End: 1883
• Publication Date: 2021-02-19
• Subjects: autophagy -- batch -- CHO -- fed‐batch -- recombinant protein production; Biotechnology -- Periodicals; Bioengineering -- Periodicals; 660.6
• DOI: 10.1002/bit.27703
• Languages: English
• ISSNs: 0006-3592

Abstract

Abstract: 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. Abstract : Autophagy ('self‐eating') is a biological process that allows cells to mitigate the impact of stresses such as nutrient deprivation. Braasch and colleagues have investigated CHO cell autophagy induction by an autophagy‐inducing peptide (AIP) derived from the autophagy protein Beclin 1. They have established that AIP can substantially increase antibody production in CHO cell batch and fed‐batch cultures. These findings provide compelling evidence supporting the further development of AIP and related peptides as defined medium additives to increase therapeutic protein manufacturing.