biostudies-literatureUnknown6(1)Wang LClinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF). Multi-gene-edited 70CAR-iNK cells exhibit robust cytotoxicity against a wide range of tumors. In vivo xenograft models further demonstrate their potency in effectively targeting lymphoma and renal cancers. Furthermore, we find that recipient alCell reports. Medicine101889https://www.ebi.ac.uk/biostudies/studies/S-EPMC11866492biostudies-literatureCD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.PMC11866492Shen LHu YLiang XWang DHuang HMo GWang KWang LZhang PZhao MShao YMo ZJia XWang YSong XZhou LChen NXu MYang LFeng YZhou YZeng WHe XHu KYue YHong RfalseCD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.Clinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF). Multi-gene-edited 70CAR-iNK cells exhibit robust cytotoxicity against a wide range of tumors. In vivo xenograft models further demonstrate their potency in effectively targeting lymphoma and renal cancers. Furthermore, we find that recipient al2025-01-01T00:00:00Z2025 Jan2026-06-02T18:15:54.253Z2025-04-04T00:06:18.136ZS-EPMC118664923979357210.1016/j.xcrm.2024.101889