A stochastic model of T cell expansion in activating micro-rod scaffolds and its continuum limit: Importance of IL-2 loading and scaffold homogeneity

Abstract

T cells are immune cells that are known to be effective at killing cancer cells, however, an individual patients tumour-specific T cell counts are often insufficient to control cancer growths. Adoptive T cell therapy aims to address this by activating and expanding highly effective T cells ex vivo before injecting them into the patient to employ their cancer-killing functions. Recent experimental setups using activating micro-rod scaffolds have significantly improved T cell expansion over conventional methods, but there is still much to understand regarding the factors that maximise the expansion of functional T cells in these scaffolds. We present a stochastic agent-based model of T cell expansion alongside its continuum limit to simulate the average interactions between T cells and micro-rods, which enable us to explore several behaviours of the experimental system. Stochastic simulations demonstrate that T cell expansion is driven by activated cell clusters around micro-rods. Using our spatial models and a mean-field approximation, we discover that this cluster-driven expansion is most supported by scaffolds with initially homogeneous micro-rod concentrations. Our simulations also reveal that loading the T cell growth factor, interleukin-2 (IL-2), into micro-rod pores for secretion significantly prolongs expansion compared to the more conventional method of IL-2 supplementation.