Jie Fu1,2, Fang Wang2,3, Li-Hou Dong1,2, Mei-Jing Xing3, Xue Cheng3, Su Wei3, Jing-Zhi Xu3, Min Han3, Kelly Dong3, Hai-Feng Song1,2. 1. State Key Laboratory of Proteomics, Beijing Institute of Lifeomics, Beijing 102206, PR China. 2. New Drug Evaluation Platform, National Engineering Research Center for Protein Drugs, Beijing 102206, PR China. 3. Immunoassay Department, United-Power Pharma Tech Co. Ltd, Beijing 102206, PR China.
Abstract
Aim: The reliable measurement of receptor occupancy (RO) provides informative data for efficacy and safety evaluation. This study aimed to assess factors affecting RO measurement of anti-PD-1 antibodies in clinical studies. Materials & methods: RO performance was assessed using different T-cell activation markers measured by flow cytometry. The validated methodology was then used in support of a clinical study. Results: The optimized active cell population was comprised of CD45RO+ or CD45RA- T cells. The bioanalytical method was validated for inter- and intra-assay precision (coefficient of variation ≤30%) and sample storage stability for 3 days. Consistent RO saturation was observed in Phase Ia clinical trial, although receptor regulation appeared to be different. The formation of anti-drug antibodies had markedly influenced pharmacokinetics and RO. Conclusion: RO measurement in combination with pharmacokinetics and anti-drug antibodies data could allow the integrated evaluation and better understanding of efficacy and safety.
Aim: The reliable measurement of receptor occupancy (RO) provides informative data for efficacy and safety evaluation. This study aimed to assess factors affecting RO measurement of anti-PD-1 antibodies in clinical studies. Materials & methods: RO performance was assessed using different T-cell activation markers measured by flow cytometry. The validated methodology was then used in support of a clinical study. Results: The optimized active cell population was comprised of CD45RO+ or CD45RA- T cells. The bioanalytical method was validated for inter- and intra-assay precision (coefficient of variation ≤30%) and sample storage stability for 3 days. Consistent RO saturation was observed in Phase Ia clinical trial, although receptor regulation appeared to be different. The formation of anti-drug antibodies had markedly influenced pharmacokinetics and RO. Conclusion:RO measurement in combination with pharmacokinetics and anti-drug antibodies data could allow the integrated evaluation and better understanding of efficacy and safety.
Authors: Xiao L Chang; Helen L Wu; Gabriela M Webb; Meenakshi Tiwary; Colette Hughes; Jason S Reed; Joseph Hwang; Courtney Waytashek; Carla Boyle; Cleiton Pessoa; Andrew W Sylwester; David Morrow; Karina Belica; Miranda Fischer; Scott Kelly; Nader Pourhassan; Rachele M Bochart; Jeremy Smedley; Christopher P Recknor; Scott G Hansen; Jonah B Sacha Journal: Front Immunol Date: 2021-11-19 Impact factor: 8.786
Authors: Fabian Junker; Pratiksha Gulati; Uwe Wessels; Stefan Seeber; Kay-Gunnar Stubenrauch; Laura Codarri-Deak; Christoph Markert; Christian Klein; Priscila Camillo Teixeira; Henry Kao Journal: Cytometry A Date: 2021-03-18 Impact factor: 4.355