Treatments that silence mast cells
MCs express several inhibitory receptors 105. Their ligand engagement inhibits MC activation and degranulation, thereby silencing MCs. Inhibitory MC receptors, including Siglec-8 and CD200Ra, and therapeutic antibodies that engage them are currently under development for CU (Figure 4). The Siglec-8-targeted antibody AK002 inhibits MC activation (and depletes eosinophils) and showed promising results in the treatment of omalizumab-naïve and omalizumab-refractory CSU, symptomatic dermographism, cholinergic urticaria, and systemic mastocytosis. The CD200Ra-targeted antibody LY3454738 is also under development for CU.