Multiplexing of receptor occupancy measurements for pharmacodynamic biomarker assessment of biopharmaceuticals.

ABSTRACT:

Background

Receptor occupancy (RO) assays measure drug target engagement, and are used as pharmacodynamic (PD) biomarkers. RO assays are commonly performed by flow cytometry and often require multiplexing for assessment of multiple PD biomarkers when specimen volumes are limited. We present multiplexed RO assays for an IGF1R-EGFR bispecific antibody (Bs-Ab) and a CTLA4-Ig recombinant fusion protein to demonstrate key considerations for accurate RO assessment.

Methods

RO in cynomolgus monkeys was determined in whole blood using flow cytometry. Free and total receptors were measured using anti-receptor fluorescence-labeled detection reagents, competitive and noncompetitive to drug, respectively.

Results

RO of IGF1R was examined as PD for Bs-Ab, since IGF1R was expressed

SUBMITTER: Vainshtein I 

PROVIDER: S-EPMC5057311 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature