Dual gene deletion improves engineered T cells in tumour models

Researchers reporting in Nature found that deleting both NR4A1 and SOCS3 improved engineered T cells' antitumour performance across different tumour models. The combination outperformed several benchmark modifications involving one or two genes in T cells and CAR-T cells, which are engineered to recognize cancer targets. The team identified the pair through a high-throughput screen that tested two gene deletions together in living organisms. The modified cells showed higher metabolic fitness and mitochondrial activity, alongside long-term tumour control without compromising the safety features assessed. The findings establish a preclinical engineering approach rather than clinical efficacy. Yale University has filed a patent application.