Modelling and simulation of Rosenberg-type adoptive cellular immunotherapy

Abstract

A mathematical model is developed to describe the process of adoptive cellular immunotherapy (ACI) using the scheme of Rosenberg and other investigators. The model exhibits the dynamics of tumour cells as well as the time evolution of the tumoricidal immunocytes, such as ex vivo interleukin-2 (IL-2) expanded natural killer (NK) cells, lymphokine activated killer (LAK) cells, tumour derived activated cells (TDAC), and interferon-gamma (IFN-γ) activated killer monocytes (AKM). The model is described mathematically by a system of nonlinear functional-differential equations. Computer simulations based on the model equations are performed using parametric configurations analogous to the protocols used in the clinical trials. The model elucidates explicitly the effects of time delays, effector immunocyte-to-tumour cell ratio, tumour growth parameters, and other critical variables on the prognosis, and the therapeutic efficacy of adoptive cellular immunotherapy.