CISH knockout iNK cells

CISH knockout iNK cells are an allogeneic, off-the-shelf cell therapy consisting of natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs) that have been genetically modified using CRISPR/Cas9 technology to delete the *CISH* (cytokine-inducible SH2-containing protein) gene. CISH is a member of the suppressor of cytokine signaling (SOCS) family and acts as a potent negative regulator of interleukin-15 (IL-15) signaling in NK cells. By knocking out CISH, these cells exhibit enhanced JAK-STAT signaling, improved metabolic fitness (characterized by increased glycolysis and oxidative phosphorylation), and superior in vivo persistence. This modification significantly boosts the cells' cytotoxic activity against a broad range of hematological malignancies and solid tumors, making them a promising candidate for cancer immunotherapy. The technology is primarily associated with ONK Therapeutics, which holds foundational intellectual property for this approach.

Other names

CISH-KO iNK cellsCISH-KO iPSC-NK cellsCISH knockout induced pluripotent stem cell-derived natural killer cells