Nature Biomedical Engineering, Published online: 09 September 2026; doi:10.1038/s41551-026-01792-7 Generative artificial intelligence (AI) has revolutionized protein engineering and has enabled de novo design of protein binders against dozens of target antigens. Our study combines AI-assisted binder design, binder integration into chimaeric antigen receptor (CAR) constructs and scalable in vitro and in vivo cell models to infer amino acid sequences and protein structures of designed binders that might facilitate efficacious CAR T cell therapies.