Autophagy-inducing Peptide Increases CHO Cell Monoclonal Antibody
Production in Batch and Fed-batch Cultures
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.