[BEBPA USA 2017] Novel, Improved Cell-Based Assays to Enable Immunotherapy Drug Development for Checkpoint Receptors

Version:: 20710
File Name/Number:: 2017 BEBPA USA
Year:: 2017

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Regulation of immune responses is tightly controlled through a balance of co-stimulatory and
inhibitory checkpoint receptors, often exploited by many cancers. Therefore, therapeutics that
block inhibitory receptors or activate immunostimulatory checkpoint receptors have proved to
be powerful agents to restore anti-tumor immune responses. However, developing drugs targeting these checkpoint proteins has proved to be quite challenging as cell-based assays used to screen for functional drugs are often difficult to create, involve the use of human primary cells, and have long, complicated protocols. Here, we present data for several new PathHunter®
Checkpoint assays that target clinically relevant co-inhibitory and co-stimulatory checkpoint
receptors using the industry-validated enzyme fragment complementation (EFC) technology.
The PathHunter assays measure receptor activation and signaling for co-stimulatory receptors
and co-inhibitory receptors. These assays enable the development of relevant therapeutics,
enabling rapid and sensitive screening of biologics and small molecules. Further, the robustness
and reproducibility of these assays lend themselves well to use in lead optimization, relative
potency, and QC lot release testing of immunotherapy drugs. These mechanism of actionbased,
biologically relevant, cell-based assays do not require human primary cells and have an
easy-to-use protocol, providing a highly sensitive response in less than 5 hours. Here, we present data for assays targeting a number of clinically important immunotherapy targets, including PD-1 (with PD-L1 and PD-L2), CTLA4, OX-40, CD27, HVEM, BTLA, 4-1BB, and CD40.