View All PostersP2017
Detection of Caspase-3/7 Activity in Human Serum & Plasma as a Potential Biomarker of Apoptotic Cell Death Using the Promega Caspase-Glo® 3/7 AssayPresenter Matthew Peach, Amgen, USA
Additional Authors: Feng Cai, Paula Kaplan-Lefko, Yongmei Gan, Guang Chen, Yang Pan, and Ren XuInduction of apoptotic cell death in cancer cells is a major strategy in developing novel therapeutics in oncology. Apoptotic stimuli activate caspase-3 and caspase-7 (caspase-3/7), proteases that cleave cellular substrates leading to cell death. Measurement of caspase-3/7 activities in easily accessible patient samples, such as serum or plasma, provides a viable option for conducting exploratory biomarker studies for apoptosis in clinical trials. To be effective, the assay to measure these activities must be sensitive and specific. The Promega Caspase-Glo® 3/7 assay is a homogeneous assay that generates a caspase-3/7 dependent chemiluminescent signal that provides selective and sensitive detection of caspase-3/7 activity. We have comprehensively optimized, characterized and qualified this enzymatic assay to detect caspase-3/7 activity in human serum and plasma. The assay has also been automated to increase throughput and reduce inter-operator variability. Additionally, we have demonstrated in pre-clinical mouse models that significant increases in caspase-3/7 activity after treatment with apoptosis inducing molecules can be detected. These increases are both concentration and time dependent. The assay has been employed in exploratory clinical biomarker studies to support clinical trials in oncology. Results from these studies may allow us to ascertain the biological activity of novel apoptosis inducing agents in human subjects as well as allow us to explore relative therapeutic efficacy with dose.