Dr Jimit Shah delivered a presentation outlining significant advancements in engineered host cell lines for high-titre biopharmaceutical production. The Sartorius Cell and Development Centre, based in Ulm, Germany, has established itself as a leader in cell and development projects, completing over 300 customer projects and supporting more than 80 molecules in clinical trials, with eight receiving market approval.
Shah began by describing the centre’s proprietary cell line development (CLD) platform, which starts with antibody sequence synthesis and cloning, followed by transfection into host cells, metabolic selection, and single-cell cloning. The use of a semi-automated cell selector device, equipped with robotic arms and an inbuilt microscope, enables precise single-cell cloning and robust traceability, which is crucial for regulatory compliance. This system also collects extensive growth and productivity data, which is analysed using machine learning algorithms to predict high-performing clones early in the process.
The core of the presentation focused on the identification and validation of molecular targets for genetic engineering. Shah’s team adopted a targeted approach, aiming to knock out energy-intensive endogenous host proteins to redirect cellular resources towards the production of the desired protein. Through mass spectrometry and data mining, 77 molecular targets were identified and individually validated. Most targets had no impact or a negative effect, but one knockout significantly improved protein titres.
Building on this, the centre generated new engineered host cell lines, narrowing hundreds of clones to the top 35 based on monoclonality and genetic characterisation. These clones demonstrated superior productivity and stability compared to wild-type hosts, with lower peak cell densities but higher protein yields. The best-performing clone was further tested across various protein modalities, confirming reproducibility and enhanced cell-specific productivity.
Ongoing work includes comprehensive CLD campaigns, stability studies over 70 generations, and scale-up experiments in bioreactors. The engineered host cells consistently show improved stability and productivity, validating their robustness for industrial applications. Shah concluded by acknowledging the collaborative efforts of product development, operations, quality, regulatory, and research teams, emphasising the centre’s commitment to continuous innovation in cell line engineering.
