Mathematical modeling unveils the timeline of CAR-T cell therapy and macrophage-mediated cytokine release syndrome
Fig 3
Identifying mechanisms driving therapy phases. A For each patient model fit, the distinct phases for CAR-T (green) and tumor (red) cell responses are identified and the characteristic slope is calculated and compared with the patient-specific mechanistic parameter driving the corresponding phase. B-H Comparison between the calculated slope and the mechanistic parameter for each phase and each patient. B Distribution phase: the calculated slope is the minimum (negative) slope of CAR-T cells, the mechanistic parameter is . C Expansion phase: the calculated slope is the maximum (positive) slope of CAR-T cells, the mechanistic parameter is κ −
. D Contraction phase: the calculated slope is the minimum (negative) slope of CAR-T cells, the mechanistic parameter is
. E Persistence phase: the calculated slope is the maximum (negative) slope of CAR-T cells, the mechanistic parameter is
. F Transient phase: the calculated slope is the maximum (positive) slope of tumor cells, the mechanistic parameter is ρ. G Shrinkage phase: the calculated slope is the minimum (negative) slope of tumor cells, the mechanistic parameter is ρ − γ. H Response phase: the calculated slope is the maximum (positive) slope of tumor cells for relapse patients only, the mechanistic parameter is ρ.