Treatments that reduce mast cell numbers
The KIT receptor is the key driver of MC differentiation, migration, proliferation and survival. The inhibition of KIT or SCF leads to MC apoptosis and reduced MC numbers. Compounds that target KIT or SCF are currently explored for the clinical development in MC-driven diseases including CU and mastocytosis 106. For example, the antibody CDX-0159, which specifically binds the extracellular dimerization domain of KIT, was shown to induce profound and sustained suppression of plasma tryptase, indicative of systemic MC ablation. CDX-0159 is currently under development for CU. Examples for the development of oral KIT-targeted treatments include Imatinib, Nilotinib, Midostaurin, and Avapritinib, all of which show efficacy in mastocytosis linked to reductions in MCs and/or serum tryptase levels.