iPSC-derived NK cells with regulatable CXCR4

iPSC-derived NK cells with regulatable CXCR4 represents an advanced cellular immunotherapy utilizing natural killer (NK) cells generated from induced pluripotent stem cells (iPSCs). These iNK cells are genetically engineered, often through CRISPR-based methods, to express the C-X-C chemokine receptor type 4 (CXCR4) in a controlled, regulatable manner. This regulatable expression is critical because constitutive high expression of CXCR4 during the iPSC differentiation process can impede their development into functional hematopoietic stem cells and subsequently NK cells. The primary objective of this modification is to significantly enhance the chemotaxis and infiltration of the iNK cells into the bone marrow, a site often affected by hematologic malignancies. By improving bone marrow homing via CXCR4's interaction with its ligand stromal-derived-factor-1 (SDF-1), these engineered iNK cells demonstrate superior cytotoxic activity against bone marrow-resident tumors, particularly in conditions like relapsed or refractory acute myeloid leukemia (R/R AML). The therapeutic potential of these cells can be further amplified by co-engineering them with chimeric antigen receptors (CARs) to specifically target tumor antigens.