Receptor occupancy assessment and interpretation in terms of quantitative systems pharmacology: nivolumab case study.

ABSTRACT: Receptor occupancy assays applied in clinical studies provide insights into pharmacokinetic-pharmacodynamic relationships for therapeutic antibodies. When measured by different assays, however, receptor occupancy results can be controversial, as was observed for nivolumab, a monoclonal antibody targeting programmed cell death 1 (PD-1) receptor. We suggested an explanation of results obtained and a mechanistic approach based on specific features of the receptor occupancy assays: measurement of the free or bound receptor, normalized to the baseline or at each time point. The approach was evaluated against controversial clinical data on PD-1 receptor occupancy by nivolumab. It was shown that receptor occupancy measured by different assays might vary substantially if the internalization rate o

SUBMITTER: Shchelokov D 

PROVIDER: S-EPMC9762804 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature