Effect of costimulatory domains on CAR-NK cell activity using a CD-70-directed CAR
Acharya S, Basar R, Daher M, et al. CD28 Costimulation Augments CAR Signaling in NK Cells Via the LCK/CD3Z/ZAP70 Signaling Axis. Cancer Discovery. 2024; (doi: 10.1158/2159-8290.CD-24-0096
Chimeric antigen receptor(CAR)-engineered natural killer (NK) cells designed with a CD28 costimulatory domain have superior anti-tumor efficacy and long-term cytotoxicity, research indicates. Using a CD70-directed CAR, investigators demonstrated that the co-stimulatory molecule CD28, when tied to CD3Z, forms a platform that recruits LCK, ZAP70, and other important kinases. The result is a signaling cascade that improved CAR-NK cell function in models of hematologic and solid tumors. CD28 is not found organically in mature NK cells, but the findings suggest introducing it into NK-based CARs may have positive implications for the advancement of cancer immunotherapy.