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Autophagy-inducing Peptide Increases CHO Cell Monoclonal Antibody Production in Batch and Fed-batch Cultures
  • Katrin Braasch,
  • Marko Kryworuchko,
  • James M. Piret
Katrin Braasch
University of British Columbia
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Marko Kryworuchko
BC Centre for Disease Control
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James M. Piret
University of British Columbia
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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 IgG1. Interestingly, the addition of 1 to 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 2-fold increase in volumetric productivity 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.

Peer review status:Published

12 Sep 2020Submitted to Biotechnology and Bioengineering
12 Sep 2020Submission Checks Completed
12 Sep 2020Assigned to Editor
14 Sep 2020Reviewer(s) Assigned
08 Oct 2020Editorial Decision: Revise Major
08 Oct 2020Review(s) Completed, Editorial Evaluation Pending
30 Nov 20201st Revision Received
30 Nov 2020Assigned to Editor
30 Nov 2020Submission Checks Completed
13 Dec 2020Reviewer(s) Assigned
12 Jan 2021Review(s) Completed, Editorial Evaluation Pending
12 Jan 2021Editorial Decision: Revise Minor
25 Jan 20212nd Revision Received
25 Jan 2021Assigned to Editor
25 Jan 2021Submission Checks Completed
25 Jan 2021Review(s) Completed, Editorial Evaluation Pending
25 Jan 2021Editorial Decision: Accept
May 2021Published in Biotechnology and Bioengineering volume 118 issue 5 on pages 1876-1883. 10.1002/bit.27703