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

Abstract T cells are immune cells that are known to be effective at fighting cancer. However, tumour-specific T cell counts are often insufficient to control cancer growths. Adoptive T cell therapy aims to leverage the cancer-killing functions of the immune system by activating and expanding highly effective T cells ex vivo before injecting them into a cancer patient. Recent experimental setups in which T cells are cultured within activating micro-rod scaffolds have achieved significantly improved yields compared with previous methods. There is still much to understand regarding the factors that maximize the expansion of T cells in these scaffolds. In this paper, 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. Our numerical simulations demonstrate that expansion is driven by activated T cells concentrated around micro-rods. Activation is initially fastest in scaffolds with homogeneous micro-rod concentrations, and our results suggest that rapid expansion could be further supported by the gradual movement of micro-rods and cells into heterogeneous clusters. Our simulations reveal that loading the T cell growth factor interleukin-2 into micro-rods significantly prolongs expansion compared with the conventional method of supplementing interleukin-2 into the culture medium.