Autophagy induction boosts biotherapeutic protein productivity in industrial cell cultures

Significance 

The demand for biopharmaceutics to treat a variety of diseases including infection, cancer, and autoimmune disorders, continues to grow. These include various monoclonal antibodies (mAbs), hormones, and other proteins, all of which have a wide range of applications. The majority of such proteins, including mAbs, are produced in genetically engineered Chinese Hamster Ovary (CHO) cells. This is largely due to the suitability of CHO cells for use in large-scale industrial settings, having high productivity, well-characterized and consistent growth phenotypes, reduced susceptibility to infections by human viruses, and the capacity to generate proteins with human-compatible glycosylation patterns. However, meeting the increasing demand for biotherapeutics by the biotechnology sector remains a challenge, and this drives manufacturing process innovation. Strategies aim at optimizing protein expression to achieve higher yields and more rapid recombinant protein production, along with high product quality and low manufacturing costs. Recently, autophagy (self-eating), a process colloquially referred to as the garbage disposal unit of the cell because of its critical role in eliminating damaged or superfluous proteins and organelles, has shown impressive promise as a strategy to enhance recombinant protein productivity. In a new study, Drs. Katrin Braasch, James M. Piret, and Marko Kryworuchko, Canadian scientists from Michael Smith Laboratories, the University of British Columbia, and the BC Centre for Disease Control, respectively, demonstrate this using a novel autophagy-inducing peptide (AIP) derived from a key autophagy-related protein named Beclin 1. Interestingly, supplementing growth medium with the AIP (at 1 to 4 µM) in CHO cell cultures, was found to increase recombinant IgG protein concentration as much as 2-fold compared to controls. Therefore, the AIP and its unique potential for bioprocess refinement through autophagy activation, is of particular interest to the industrial biotechnology sector, and clearly merits further investigation.

Reference

Braasch, K., Kryworuchko, M., & Piret, J. M. (2021). Autophagy-inducing peptide increases CHO cell monoclonal antibody production in batch and fed-batch cultures. Biotechnology and Bioengineering, 118(5), 1876–1883. https://doi.org/10.1002/bit.27703

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