Speaker
Description
Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of certain haematological malignancies, yet relapse and primary resistance remain common. Although CAR T cells circulate systemically, their ability to activate, persist and eliminate target cells varies across tissues, suggesting that microenvironmental context plays a key role in therapeutic outcome.
Understanding these dynamics requires integrating experimental observations with mechanistic modelling across biological scales. Experimental systems provide essential measurements of CAR T behaviour, but many mechanistic hypotheses and treatment strategies cannot be directly tested in vivo. Agent-based models (ABMs) offer a complementary approach by representing cell-level interactions and emergent population dynamics, enabling controlled exploration of tissue contexts, dosing strategies and treatment schedules while supporting the principles of the 3Rs (Replace, Reduce, Refine).
Here I present an integrative framework linking multiscale experiments with mechanistic modelling to study CAR T dynamics across anatomical sites. Central to this effort is the development of an organ-to-organ atlas capturing tissue-specific CAR T behaviour across multiple organs. Integrated with an ABM as a mechanistic engine, these data enable calibration of tissue-aware virtual experiments and lay the groundwork for patient-specific digital twins capable of forecasting treatment responses in silico.
