Speaker
Description
The rapid expansion of immunotherapies in Oncology has increased the need for quantitative models that can understand their mechanisms and limitations. T cell engagers (TCEs) are an emerging therapeutic class that bind both T cell receptors and tumour associated antigens to promote immunological synapse formation and targeted cytotoxicity. Despite growing clinical success, their efficacy is constrained by challenges such as treatment limiting toxicities, T cell exhaustion, and the hook effect. Mathematical and computational modelling offers a powerful means to understand these processes and support the rational optimisation of TCE design. We present an agent-based multiscale modelling framework using PhysiCell to investigate how binding kinetics, receptor expression, and spatial heterogeneity within the tumour microenvironment influence TCE function. By integrating mechanistic binding rules with spatially explicit cell–cell interactions, the model enables systematic exploration of trimer formation dynamics, the emergence of the hook effect, and their combined impact on tumour cell killing.
