A hybrid PKPD agent-based model of the tumour immune interaction: effects of anti-cancer combination therapy

We have developed a three dimensional hybrid multi-scale agent-based ODE PDE model including tumour immune interaction, cell cycle phases, oxygen and drug diffusion dynamics, the pharmacodynamics of chemotherapy, targeted therapies, immunotherapy, radiotherapy and the respective systemic exposure levels of pharmacological treatments (described by pharmacokinetic modelling). The aim of this model is to support a more detailed understanding of the spatial-temporal dynamic interactions between cancer cells, the relevant immune cells, and especially targeted therapies' molecular moieties, which are all expected to interact simultaneously in the tumour microenvironment. This interaction can then be further investigated in the context of combination therapies, thus making some inroads in the mechanistic understanding of positive and negative synergies when multiple therapies are administered within this complex system. The key scientific question this work addresses is the role of temporal sequencing in combination therapies, which require the simultaneous modelling of many relevant components of the system to be properly understood.