biostudies-literatureZhi LHenan Program for Science and Technology DevelopmentTalent Support Program of Xinxiang Medical University337https://www.ebi.ac.uk/biostudies/studies/S-EPMC11853679biostudies-literatureUnknown25(1)<h4>Background</h4>Chimeric antigen receptor (CAR) engineered natural killer (NK) cells have shown their efficacy and superiority against cancer and possess the potential to become off-the-shelf immunotherapy products. Nonetheless, some challenges associated with CAR-NK cells still exist including inhibitory receptor engagement, antigen escape, and inadequate activation.<h4>Methods</h4>Given this, based on the concept of synthetic biology, we rationally designed a novel dual-targeted CAR (dtCAR), primarily comprising PD-L1 nanoantibody (PD-L1^Nb) and NKG2D as the ectodomain, transmembrane and cytoplasmic domains (CP) of CD28, and the CP of 4-1BB and CD3ζ. NK92 cells were engineered to express this third-generation of dtCAR. We then elucidated the role of dtCAR-modified NK92 cellsBMC cancerCAR-NK cells with dual targeting of PD-L1 and MICA/B in lung cancer tumor models.PMC11853679XYBSKYZZ201924232102311042Gao QZhi LZhang ZHe WNiu ZGuo CZhu WWang YShang CfalseCAR-NK cells with dual targeting of PD-L1 and MICA/B in lung cancer tumor models.<h4>Background</h4>Chimeric antigen receptor (CAR) engineered natural killer (NK) cells have shown their efficacy and superiority against cancer and possess the potential to become off-the-shelf immunotherapy products. Nonetheless, some challenges associated with CAR-NK cells still exist including inhibitory receptor engagement, antigen escape, and inadequate activation.<h4>Methods</h4>Given this, based on the concept of synthetic biology, we rationally designed a novel dual-targeted CAR (dtCAR), primarily comprising PD-L1 nanoantibody (PD-L1^Nb) and NKG2D as the ectodomain, transmembrane and cytoplasmic domains (CP) of CD28, and the CP of 4-1BB and CD3ζ. NK92 cells were engineered to express this third-generation of dtCAR. We then elucidated the role of dtCAR-modified NK92 cells2025-01-01T00:00:00Z2025 Feb2026-05-24T03:15:31.198Z2025-04-04T02:11:02.684ZS-EPMC118536794000097410.1186/s12885-025-13780-2