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

We have developed a three dimensional hybrid multiscale 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 understanding of the spatial-temporal dynamic interactions between cancer cells, the relevant immune cells, and targeted therapies’ molecular moieties, which interact simultaneously in the tumour microenvironment. This interaction is 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. This work addresses the role of temporal sequencing in combination therapies, which requires the simultaneous modelling of multiple system components.