Fabien Vincent, Former Pharmacology Lab Head, Pfizer covered the limitations of using traditional cell lines in drug discovery. More precisely, he highlighted their significant chromosomal abnormalities and limited ability to replicate true human biology. Vincent called for a paradigm shift: making primary human cells the default for research programmes, with cell lines used only when primary cells are not feasible.
A central concern he discussed was donor-to-donor variability. While signal strength (Emax) can vary between donors, key pharmacological metrics such as IC50 and EC50 remain consistent. This means that, despite variability in response magnitude, the core pharmacological data needed for drug screening is robust and reproducible across donors.
The presentation also detailed the logistical evolution over 15 years, showing that sourcing and working with primary human cells is now practical and scalable. Advances in the life sciences industry have made a wide range of primary cells such as patient-derived and iPS cells readily available. Vincent’s laboratory developed over 30 primary human cell-based assays, supporting numerous small molecule programmes, particularly in immunology and inflammation.
A profound analysis of these assays revealed that, although there is variability in maximum response between donors, the pharmacological potency (IC50/EC50) is highly reproducible. The only notable caveat is that all data were obtained from healthy donors; patient-derived cells may show greater variability, which could be informative for disease-specific research.
The impact of this approach has been significant: primary cell-based assays have increased confidence in structure-activity relationship (SAR) data and contributed to the development of clinical candidates, including two FDA-approved drugs. Vincent’s closing remarks stated that physiologically relevant assays using primary cells improve the odds of success in drug discovery, and donor-to-donor variability, while present, does not undermine the reliability of pharmacological screening outcomes.
