The invention features nucleic acid constructs encoding chimeric immunoreceptors (CIRs) that are useful for treating a KIT+ associated disease in patients. In general, the CIRs contain an extracellular domain (e.g., a KIT-ligand (KL) or stem cell factor (SCF)) which interacts with and destroys KIT+ tumor cells, a transmembrane domain, and a cytoplasmic domain for mediating T cell activation (e.g., CD3 zeta and/or the domain of CD28). The invention also features the use of the nucleic acid constructs and/or host cells expressing CIRs in the treatment of a KIT+ associated disease, in particular gastrointestinal stromal tumor (GIST).
