Fig. 5

A summary of genetically modified iPSC-NK therapies. iPSC-NK cells have been genetically engineered to overcome the various limitations associated with NK therapies. Attempted modifications include mutated versions of the CD16 receptor to inhibit cleavage by the ADAM17 protease, fused cytokine receptor-ligand receptors to improve in vivo persistence, CARs to improve anti-tumor cytotoxicity, receptor knockout to prevent fratricide from combinatorial antibody treatments, and recombinant receptors to increase NK cytotoxicity outside the context of cancer. Another approach has been to target checkpoint inhibitors through deletion of the CISH gene