A Quantitative Systems Pharmacology Model of T Cell Engager Applied to Solid Tumor

Cancer immunotherapy has recently drawn remarkable attention as promising results in the clinic have shown its ability to improve the overall survival, and T cells are considered to be one of the primary effectors for cancer immunotherapy. Enhanced and restored T cell tumoricidal activity has shown great potential for killing cancer cells. Bispecific T cell engagers (TCEs) are a growing class of molecules that are designed to bind two different antigens on the surface of T cells and cancer cells to bring them in close proximity and selectively activate effector T cells to kill target cancer cells. New T cell engagers are being investigated for the treatment of solid tumors. The activity of newly developed T cell engagers showed a strong correlation with tumor target antigen expression. However, the correlation between tumor-associated antigen expression and overall response of cancer patients is poorly understood. In this study, we used a well-calibrated quantitative systems pharmacology (QSP) model extended to bispecific T cell engagers to explore their efficacy and identify potential biomarkers. In principle, patient-specific response can be predicted through this model according to each patient’s individual characteristics. This extended QSP model has been calibrated with available experimental data and provides predictions of patients’ response to TCE treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1208/s12248-020-00450-3) contains supplementary material, which is available to authorized users.