CHIMERIC ILT RECEPTOR COMPOSITIONS AND METHODS

Provided are chimeric ILT receptors (CIRs) that include a targeting region from ILT2 or ILT4, a transmembrane domain, and an intracellular domain (ICD). The ICD includes a signaling region (e.g., CD3 zeta (CD3ζ)) and optionally a costimulatory region (e.g., CD28, 4-1BB, OX40, and the like). Also provided are nucleic acids (e.g., expression vectors) encoding a subject CIR, and genetically modified cells (e.g., immune cells such as NK cells, T cells, iNKT cells, macrophages, and the like) expressing a subject CIR. For example, provided are genetically modified immune cells such as NK cells that include a nucleic acid encoding an ILT2 or ILT4 CIR. The subject CIRs are designed to activate cytotoxicity by immune cells such as NK cells, T cells, iNKT cells and macrophages against HLA-G expressing cancers.