Immunotherapy is emerging as one of the most promising approaches in cancer treatment, allowing specific targeting of cancer cells from CD8+ T Lymphocytes based on surface marker expression. In vitro characterization of the efficacy and potency of BiTEs or CAR T-Cell constructs is a necessary step before moving to animal models and Phase I and II clinical studies. In this study we present the optimization of several protocols to analyze cancer immunotherapy reagents using an impedance-based platform. The platform allows detection of cell adhesion and cell death trough monitoring the change in conductance of microelectrodes embedded on the bottom of the culture dish. Because cell adhesion over the electrodes alters the conductivity of the surface, any change in cell morphology, adhesion or number is detected as alteration of an impedance-related parameter called Cell index (Ci). Furthermore, because the platform avoid the use of any chemical label or sample processing, it allows continuous monitoring of cell activity. Dose-responses curves of BiTEs antibodies against epithelial tumor cell lines with a range of expression of the EpCAM antigen show correlation between surface expression level and efficacy of the constructs. Decreasing ratios between effector and target cells, in combination with longer time of monitoring reveal the efficacy of such constructs also at equivalent stoichiometric ratio. Taken together our results demonstrate higher sensitivity of the impedance-based approach over established methodologies like Chromium-51 release assay and live-cell imaging, improving and speeding up the workflow for therapy optimization.

Citation Format: Fabio Cerignoli, Jenny Zhu, Biao Xi, Leyna Zhao, Jeff Irelan, Yama Abassi. In vitro monitoring of the efficacy of cancer immunotherapy designs trough an impedance-based platform. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-B16.