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.