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.