Speaker
Description
Chimeric Antigen Receptor (CAR)-T cell therapy is revolutionising immunotherapy, and has shown significant efficacy in cancers of the blood. Experimental collaborators have observed that patterns of clone-agnostic and clone-specific resistance change sharply with immunologic pressure. We have leveraged mathematical modelling to determine which mechanisms can give rise to the experimentally observed clonal resistance profiles. We develop our models under a branching process framework, considering features such as CAR-T expansion, cytotoxic action, tumour competition, and stochastic extinction. Our modelling suggests that the observed clonal distributions are only possible in the presence of cellular competition. Calibrating the models to experimental data has presented numerous challenges. We conclude by sharing our ambitions for model calibration and highlighting the value of mathematical modelling as a framework for exploring mechanisms in the absence of explicit model calibration.
