Cell function profiling to assess clone stability
Paul D Dobson1, Karen P Coss1, Carolanne Doherty1
1Valitacell Ltd, NIBRT Foster Avenue, Mount Merrion, Blackrock, County Dublin, Ireland.
Biotechnology and Bioengineering
|March 18, 2020
Summary
Identifying stable Chinese hamster ovary (CHO) cell lines for bioproduction is challenging. A new assay, ChemStress® cell function profiling, monitors cellular pathways to find truly stable CHO clones, improving production reliability.
Area of Science:
- Biotechnology
- Cell Line Development
- Bioprocess Engineering
Background:
- Identifying stable Chinese hamster ovary (CHO) cell lines is crucial for biopharmaceutical production but challenging.
- Traditional stability trials focusing on high-level attributes can overlook underlying cellular instability, leading to the selection of suboptimal clones.
- Assessing cellular pathway stability without increasing development costs is a significant hurdle.
Purpose of the Study:
- To introduce and validate ChemStress® cell function profiling as a method to assess the internal stability of CHO cell clones.
- To develop a novel stability metric for identifying genuinely stable CHO clones during stability trials.
- To enable a deeper understanding of cell line stability beyond traditional high-level production attributes.
Main Methods:
- ChemStress® cell function profiling, a multiwell plate-based assay, was employed using a panel of chemicals to simulate bioprocess stresses.
- The assay challenged key cellular pathways in 131 CHO clones over 3 days of static culture.
- Functional responses, including titer and growth, were measured, and a novel stability metric was defined.
Main Results:
- ChemStress® profiling successfully monitored the stability of 131 CHO clones throughout real stability trials.
- A novel stability metric was defined, enabling the identification of clones that remained unperturbed across multiple cellular functions.
- The assay provided insights into internal cellular stability, going beyond superficial production metrics like titer.
Conclusions:
- ChemStress® cell function profiling offers a cost-effective method to assess the underlying stability of CHO cell lines.
- This approach allows for the selection of more robust and internally stable CHO clones for bioproduction.
- Implementing this assay enhances the reliability of cell line development by looking beneath simple titer measurements to ensure true clone stability.
