Natural killer cells don’t have to be natural born natural killer cells. In fact, mass produced natural killer cells—that is, natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs)—can be more persistent, more effective killers, report scientists based at the University of California, San Diego. These scientists say that one way to turn human iPSC-derived NK cells into uninhibited killing machines is to deprive them of a gene that encodes a crucial cytokine regulator.
Details about human iPSC-derived NK cells appeared June 11 in an article in Cell Stem Cell. The cells lack a gene called CISH, which encodes cytokine-inducible SH2-containing protein, a checkpoint or braking mechanism that is ordinarily expressed by NK cells that are stimulated by cytokines such as interleukin-15 (IL-15). Without this braking mechanism, NK cells can go on a killing spree.
According to experimental evidence, the human iPSC-derived NK have greater cytotoxic activity in vitro. They are also better at inhibiting tumor progression in vivo. Finally, they display greater metabolic fitness—just the thing to keep a killing spree going.
The article, entitled “Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-tumor Activity,” was contributed by a team of scientists led by Dan Kaufman, MD, PhD, professor of medicine in the Division of Regenerative Medicine and director of cell therapy at UC San Diego School of Medicine.
“We found that CISH-deleted iPSC-derived NK cells were able to effectively cure mice that harbor human leukemia