Scientists from the Massachusetts Institute of Technology and Harvard University have collaborated to design a novel chimeric antigen receptor natural killer (CAR-NK) cell. This type of cell can not only accurately destroy cancer cells, but also cleverly "hide and protect itself" to avoid defense attacks from the human immune system. This breakthrough is expected to solve the long-standing problem of immune rejection in cell therapy and improve treatment effectiveness. The relevant paper was published in the latest issue of the journal Nature Communications. Natural killer (NK) cells are important members of the human immune defense, responsible for identifying and eliminating cancer cells and virus-infected cells. At present, CAR-NK therapy usually requires extracting NK cells from the patient's body, genetically engineering them to express chimeric antigen receptors (CARs) that can recognize cancer cell specific markers, and then amplifying them in vitro for several weeks before they can be reintroduced into the patient's body. Scientists are also exploring the acquisition of NK cells from healthy donors, but the challenge is that the recipient's immune system typically sees foreign donor cells as "foreign" and clears them. To this end, the team attempted to teach the donor NK cells how to use "invisibility techniques". Experiments have shown that if HLA-1 molecules (an identity recognition protein) on the cell surface are removed, NK cells can avoid attacks from host T cells. To this end, they introduced short interfering RNAs to silence related genes and block the production of this type of protein. They also simultaneously introduced CAR genes and genes encoding PD-L1 or single stranded HLA-E (SCE) to enhance the anti-cancer ability of NK cells. All added genes are integrated into one construct, which efficiently converts donor NK cells into CAR-NK cells that are both anti-cancer and "invisible". In the experiment targeting lymphoma, the modified CAR-NK cells almost completely cleared the tumor. In contrast, NK cells that have not been modified or only carry CAR genes are rapidly cleared by the host immune system and cannot control cancer progression. Moreover, the risk of cytokine release syndrome caused by the novel CAR-NK cells is relatively low. The team predicts that CAR-NK cells may gradually replace CAR-T cells in the future. The CAR-NK therapy currently developed for other cancers can also be optimized by drawing on the gene construction strategy in this study. (New Society)