CAR-neutrophils Produced In Vivo to Treat Glioma
Published in Nature Biomedical Engineering, 2026
Recommended citation: Yun Chang, Kunming Shao, Huiyang Li, Gyuhyung Jin et al., Nature Biomedical Engineering, 2026 https://www.nature.com/articles/s41551-026-01656-0
Abstract Neutrophils are abundant circulating immune cells with important roles in the tumour microenvironment, but direct genetic programming of neutrophils has remained technically difficult. In this study, we developed a neutrophil-specific modified RNA translation platform, termed NeuSMRT, to enable chimeric antigen receptor (CAR) expression in primary neutrophils. NeuSMRT combines engineered extracellular vesicles or lipid nanoparticles for modified RNA delivery with a microRNA-responsive L7Ae:k-turn translational switch, thereby restricting CAR protein translation to neutrophils. In a syngeneic glioma model, in vivo–generated CAR-neutrophils suppressed tumour growth, prolonged survival, enhanced T cell recruitment and activation, and reduced myeloid-cell-associated immunosuppression in the tumour microenvironment. CAR-neutrophils also improved the efficacy of chemotherapy and CAR-T therapy, showed antitumour activity in a humanized glioblastoma mouse model, and demonstrated feasibility and safety in experimental dogs. Together, these findings establish NeuSMRT as a programmable neutrophil engineering platform for cancer immunotherapy.
Keywords: CAR-neutrophils, glioma, glioblastoma, cancer immunotherapy, neutrophil engineering, in vivo cell programming, modified RNA, extracellular vesicles, lipid nanoparticles, tumour microenvironment, NeuSMRT