Peptonics: a new family of cell-protecting surfactants for the
recombinant expression of therapeutic proteins in mammalian cell
cultures
Abstract
Polymer surfactants are key components of cell culture media as they
prevent mechanical damage during fermentation in stirred bioreactors.
Among cell-protecting surfactants, Pluronics are widely utilized in
biomanufacturing to ensure high cell viability and productivity.
Mono-dispersity of monomer sequence and length is critical for the
effectiveness of Pluronics - since minor deviations can damage the cells
- but is challenging to achieve due to the stochastic nature of
polymerization. Responding to this challenge, this study introduces
Peptonics, a novel family of peptide and peptoid surfactants whose
monomer composition and sequence are de-signed to achieve high cell
viability and productivity at a fraction of chain length and cost of
Pluronics. A designed ensemble of Peptonics was initially characterized
via light scattering and tensiometry to select sequences whose phase
behavior and tensioactivity align with those of Pluronics. Selected
sequences were evaluated as cell-protecting surfactants using Chinese
hamster ovary (CHO) cells expressing therapeutic monoclonal antibodies
(mAb). Peptonics IH-T1010, ih-T1010, and ih-T1020 afforded high cell
density (up to 3·107 cells·mL-1) and viability (up to 95% within 10
days of culture), while reducing the accumulation of ammonia (a toxic
metabolite) by ~10% compared to Pluronic F-68. Improved
cell viability afforded high mAb titer (up to 5.5 mg·mL-1) and extended
the production window beyond 14 days; notably, Peptonic IH-T1020
decreased mAb fragmentation and aggregation ~5%, and
lowered the titer of host cell proteins by 16% compared to Pluronic
F-68. These features can improve significantly purification of mAbs,
thus increasing their availability at lower cost to patients.