IL-6 Trans-Signaling Loop in CAR-T Cytokine Release Syndrome

Cytokine release syndrome (CRS) is the most common serious toxicity of CAR-T cell therapy, and its escalation is driven less by the CAR-T cells themselves than by a positive feedback loop: activated macrophages release IL-6, which binds soluble IL-6 receptor and signals through gp130 on cells like the vascular endothelium (trans-signaling), triggering yet more IL-6 and vascular leak. This simulator renders that loop in 3D — CAR-T cells engaging a shrinking tumor cluster, macrophages emitting IL-6 particles onto a central vessel — and lets you tune CAR-T dose, the trans-signaling gain that makes the loop self-reinforcing, and a tocilizumab (anti-IL-6R) dose that interrupts it, exactly as the real drug does in the clinic. Live readouts track serum IL-6, core temperature, the loop's instantaneous growth rate, and an ASTCT-style fever-driven CRS grade proxy.