Lunch & Learn with Promega Corporation

Advancing Functional Potency Testing for T Cell Engagers and Monoclonal Antibodies

Nicholas Hess, Associate Project Manager, Promega Corporation

The functional characterization of T cell engagers (TCEs) and monoclonal antibodies (mAbs) requires potency assays that are precise, scalable, and reflective of in vivo activity. Promega’s targeted cell killing (TCK) and cell-based reporter bioassays provide complementary approaches determining precise mode of action (MoA) studies. TCK cells provide a robust and physiologically relevant method for assessing cytotoxicity using primary immune effector cells while the cell-based reporter bioassays offer a rigorous and high-throughput approach. These complementary bioassays such as the ADCC/ADCP and T cell activation bioassays, create a comprehensive potency testing platform.

The HiBiT TCK system offers a gain-of-signal luminescence readout, eliminating background noise from spontaneous cell death of effector cells and provides quantitative measurements of antibody- and immune cell-mediated cytotoxicity. Its compatibility with a range of therapeutic modalities, including immune cell engager, Fc-engineered mAbs, and antibody drug conjugates, highlights its broad applicability. When combined with ADCC reporter and T cell activation bioassays, the TCK system enables a deeper understanding of biologic function by correlating direct cytotoxic effects with a define cell-based MoA bioassay.

We present data demonstrating the synergy between these platforms, highlighting their ability to deconvolute mechanism of action, differentiate between effector pathways, and ensure batch-to-batch consistency in drug potency testing. This integrated approach enhances the precision of biologic characterization, supporting both early-stage discovery and regulatory-compliant lot release testing.

By leveraging the complementary strengths of TCK assays and cell-based bioassays, we provide a streamlined and high-sensitivity workflow to accelerate the development of TCEs and mAbs with improved potency and specificity.