Directly reprogrammed natural killer cells for cancer immunotherapy

Efficacious and accessible sources of natural killer (NK) cells would widen their use as immunotherapeutics, particularly for solid cancers. Here, we show that human somatic cells can be directly reprogrammed into NK cells with a CD56(bright)CD16(bright) phenotype using pluripotency transcription factors and an optimized reprogramming medium. The directly reprogrammed NK cells have strong innate-adaptive immunomodulatory activity and are highly potent against a wide range of cancer cells, including difficult-to-treat solid cancers and cancer stem cells. Both directly reprogrammed NK cells bearing a cancer-specific chimeric antigen receptor and reprogrammed NK cells in combination with antibodies competent for antibody-dependent cell-mediated cytotoxicity led to selective anticancer effects with augmented potency. The direct reprogramming of human somatic cells into NK cells is amenable to the production of autologous and allogeneic NK cells, and will facilitate the design and testing of cancer immunotherapies and combination therapies. Human natural killer cells with potent anticancer activity can be directly reprogrammed from somatic cells using pluripotency transcription factors and an optimized reprogramming medium.

Automated summary

Human natural killer cells with potent anticancer activity can be directly reprogrammed from somatic cells using pluripotency transcription factors and an optimized reprogramming medium. These reprogrammed NK cells show strong innate-adaptive immunomodulatory activity and are highly effective against a wide range of cancer cells, including solid cancers and cancer stem cells. Reprogrammed NK cells, either bearing cancer-specific chimeric antigen receptors or combined with antibodies for antibody-dependent cell-mediated cytotoxicity, demonstrate selective anticancer effects with enhanced potency.